Objective To comparatively observe the effect of electroacupuncture at digestive system-related lower he-sea points on the expressions of serum interleukin-1β（IL-1 β）, tumor necrosis factor-α（TNF-α） of colon t...Objective To comparatively observe the effect of electroacupuncture at digestive system-related lower he-sea points on the expressions of serum interleukin-1β（IL-1 β）, tumor necrosis factor-α（TNF-α） of colon tissues and high mobility group box 1 protein（HMGB 1） of ulcerative colitis（UC） model rats, and to explore whether there is relative specificity of electroacupuncture at Shàngjùxū（上巨虚 ST 37）, one of lower he-sea points of large intestine, in treatment of bowel diseases. Method A total of 60 SD rats were randomly divided into control group, model group, ST 37 group, Zúsānl？（足三里 ST 36） group, Xiàjùxū（下巨虚 ST 39） group and Yánglíngquán（阳陵泉 GB 34） group. There were ten rats in each group; five were males, and five were females. UC models were established by clysis with 2, 4, 6-trinitrobenzene sulfonic acid/alcohol solution. After modeling, treatment was conducted for ten days, specimens were collected, colonic ulcers and inflammation were inspected visually and scored. The content of serum IL-1β and the expressions of TNF-α and HMGB 1 in colon were detected through ELISA. Results 1 Compared with control group, the scores of colonic ulcers and inflammation, the content of serum IL-1β and the expressions of TNF-α（except ST 37 group） and HMGB 1 were all higher（P〈0.05, P〈0.01）; 2 compared with model group, the scores of colonic ulcers in ST 36 group and ST 37 group were lower obviously（P〈0.05, P〈0.01）; the expressions of IL-1β, TNF-α and HMGB 1 in the four treatment groups were lower obviously（P〈0.01）; 3 compared with ST 37 group, the expressions of IL-1β, TNF-α and HMGB 1 in other three treatment groups were higher obviously（P〈0.05, P〈0.01）; and the scores of colonic ulcers in ST 39 group and GB 34 group were higher obviously（P〈0.05）. Conclusion 1 The score of colonic ulcers can be reduced through electroacupuncture at ST 37, ST 36, ST 39 and GB 34, which can also reduce the content of serum IL-1β and the expressions of TNF-α and HMGB 1, and effectively inhibit inflammatory response of colon caused by UC; 2 the effect trend of the four acupoints in treatment of UC is： ST 37ST 36ST 39GB 34, and electroacupuncture at ST 37 has the best effect with relative specificity.展开更多
Peyronie’s disease(PD)is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages.In this study,we aimed to compare four injectable induct...Peyronie’s disease(PD)is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages.In this study,we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD:transforming growth factor-β1(TGF-β1),fibrin,sodium tetradecyl sulfate(STS)combined with TGF-β1,and polidocanol(POL)combined with TGF-β1.The results showed that injection of TGF-β1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature.The STS+TGF-β1 combination resulted in both histological and morphological alterations,but with a high incidence of localized necrosis that led to animal death.The POL+TGF-β1 combination produced pathological changes and curvature comparable to STS+TGF-β1 and led to fewer complications.In conclusion,fibrin,STS+TGF-β1,and POL+TGF-β1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats.The POL+TGF-β1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.展开更多
BACKGROUND： Hypoxia inducible factor-1 alpha （HIF-1 （x） and erythropoietin（EPO）, possessing neuroprotective effect in the cerebral ischemia, might play an important role in the formation of cerebral ischemic tol...BACKGROUND： Hypoxia inducible factor-1 alpha （HIF-1 （x） and erythropoietin（EPO）, possessing neuroprotective effect in the cerebral ischemia, might play an important role in the formation of cerebral ischemic tolerance （IT）. OBJECTIVE：To observe the neuroprotective effect of cerebral ischemic preconditioning（IPC） of rats, and the expression and mechanism of HIF-1α and target gene erythropoietin in the brain tissue following the formation of cerebral IT. DESIGN ： A randomized and controlled observation SETTING： Department of Neurology, the Affiliated Hospital of Medical College, Qingdao University MATERIALS： Totally 84 enrolled adult healthy male Wistar rats of clean grade, weighing 250 to 300 g, were provided by the Animal Experimental Department, Tongji Medical College of Huazhong University of Science and Technology. Ready-to-use SABC reagent kit and rabbit anti-rat HIF-1α monoclonal antibody were purchased from Boshide Bioengineering Co.Ltd （Wuhan）; Rabbit anti-rat EPO monoclonal antibody was purchased from Santa Cruz Company （USA）. METHODS： This experiment was carried out in the Department of Anatomy, Medical College, Qingdao University during March 2005 to March 2006. ① The 84 rats were divided into 3 groups by a lot： IPC group （n=40）, sham-operation group （n=40） and control group （n=4）. In the IPC group, middle cerebral artery was occluded for 2 hours respectively on the 1^st, 3^rd, 7^th, 14^th and 21^st days of the reperfusion following 10-minute preischemia was made using a modified middle cerebral artery second suture method from Zea-Longa. The rats were sacrificed 22 hours after reperfusion in the end of middle cerebral artery occlusion （MCAO）. That was to say, after 10-minute preischemia, suture was exited to the extemal carotid artery and embedded subcutaneously. Middle cerebral artery was occluded again to form the second reperfusion at the set time point after reperfusion. Twenty-two hours later, rats were sacrificed; In the sham-operation group,the preischemia was substituted by sham-operation（only common carotid artery and crotch were exposed, and MCAO by suture was omitted）, and the other procedures were the same as those in the IPC group. In the control group, rats were given sham-operation twice at an interval of one day, and they were sacrificed 24 hours after the second sham-operation. ② Brain tissue was taken from the rats in each group. Cerebral infarction area of each layer was measured with TTC staining, and total cerebral infarction volume （The total cerebral infarction area of each layerxinterspace ） was calculated. After brain tissue was stained by haematoxylin-esoin （HE）, the form of nerve cells was observed under an optical microscope, and the expressions of HIF-1α（and EPO protein in the brain tissue were detected with immunohistochemical method. MAIN OUTCOME MEASURES： ①Cerebral infarction volume;②form of nerve cell; ③ the expression of HIF-1α and EPO protein in the brain tissue. RESULTS：Totally 84 rats were enrolled in the experiment. The dead rats were randomly supplied during the experiment, and finally 84 rats entered the stage of result analysis. ① Detection of cerebral infarction volume of rats in each group： Cerebral infarction volume in the IPC group was significantly smaller than that in the sham-operation group on the 1^st, 3^rd and 7^th days after reperfusion respectively [（161.2±6.9） mm^3 vs （219.9±11.2） mm^3, （134.9±9.0） mm^3 vs （218.6±13.0） mm^3, （142.9±13.7） mm^3 vs （221.3±14.2） mm^3, t=-8.924, 10.587,7.947, P〈 0.01]. ② Observation of nerve cell form of brain tissue： HE staining showed that the ischemic degree, range and cerebral edema degree of IPC group were significantly milder than those of sham-operation group. ③ The expressions of HIF-1α and EPO protein in cerebral cortex and hippocampus ： The expression of HIF-1αof IPC group was significantly higher than that of sham-operation group on the 1^st, 3^rd and 7^th days after reperfusion respectively （125.93±3.79 vs 117.65±5.60, 140.63±4.64 vs 119.33±4.26, 131.15±2.74 vs 107.60±3.89, t=2.449, 6.763,9.899,P 〈 0.05-0.01）. The expression of EPO of IPC group was significantly higher than that of sham-operation group on the 3^rd and 7^th days after perfusion respectively （141.68±3.29 vs 126.33±4.51, 138.88±2.59 vs 125.58±6.18,t=5.499,3.970, P〈 0.05）. CONCLUSION ： ①IPC can protect the never cells in rat brain and the best time to onset of cerebral IT induced by IPC is 1 to 7 days after reperfusion. ② Neuroprotective effect of cerebral IT might be related to the expression of HIF-1α and its target gene EPO.展开更多
BACKGROUND： Previous researches suggested that expression level of calbindin D28K mRNA decreased in substantia nigra （SN） of model rats with Parkinson disease （PD）, and this might be related to the decrease of an...BACKGROUND： Previous researches suggested that expression level of calbindin D28K mRNA decreased in substantia nigra （SN） of model rats with Parkinson disease （PD）, and this might be related to the decrease of anti-degeneration potentials of dopaminergic neurons. OBJECTIVE： To observe expression changes of calbindin D28K in SN dopaminergic neurons during their degeneration and death in midbrain of PD model rats. DESIGN： Completely randomized grouping design SETTING： Department of Neurobiology, Xuzhou Medical College MATERIALS＂ A total of 92 healthy male SD rats, with the age of 3 months, weighing 200-250 g, were selected from Experimental Animal Center of Xuzhou Medical College [certification： SCXK （su） 2003-0003]. Calbindin D28K（CB）, tyroxine hydroxylase （TH）, ABC kit, 6-hydroxydopamine （6-OHDA） and Nissl dyes were provided by Sigma Company, and sheep serum was provided by Beijing Zhongshan Company. METHODS： The experiment was carried out in the Neurobiological Center of Xuzhou Medical College from October 2003 to October 2004. ① With lot method, rats were divided into blank control group （n=28）, experimental control group （n=-28） and experimental group （n=36）. Rats in experimental group were injected with 6-OHDA at right corpus striatum for PD modeling; rats in experimental control group were injected with saline at the same site; rats in blank control group did not give any injections.② On the 7^th, 14^th, 21^st and 28^th days, SN segments on right midbrain from every 5 rats in experimental group were fixed, embedded with paraffin and cut into successively coronary pieces. Rats in other two groups were treated with the same methods and then stained with Nissl to show neuronal form. Meanwhile, CB and TH antibodies staining with immunohistochemistry were used to show CB containing dopaminergic neurons and dopaminergic neurons, and cells were calculated and observed under optic microscope. ③ On the 14^th and 28^th days, every 4 rats in experimental group and every 4 rats in control group were selected to obtain their brains and separate SN on the injured side. Western blot was used to detect expression of calbindin D28K, protein band was scanned with imaging equipment, and data were analyzed with LabWorks software. MAIN OUTCOME MEASURES：① On the 7^th, 14^th, 21^st and 28^th days, Nissl staining results of SN neurons and immunohistochemical staining results of CB and TH antibodies; ② On the 14^th and 28^th days, Western blot results of calbindin D28K in SN neurons, RESULTS; Among 92 rats, 2 rats in experimental group died after 1 day due to 6-OHDA injection and other 90 rats were involved in the final analysis. ①Nissl staining results： On the 7^th day of 6-OHDA injection, most neuronal somas on right SN pars compacta were shown as deep pycnosis or lysis breakage; on the 14^th and 21^st days, amount of neurons was decreased remarkably; on the 28^th day, most neurons in SN pars compacta disappeared. ② Results of immunohistochemical staining： Amount of positive neurons of calbindin D28K in right SN pars compacta was not changed on the 7^th day after 6-OHDA injection; on the 14^th day, the amount was higher in experimental group than that in both control groups （P 〈 0.01） and was decreased till the 21^st day, but it was still higher than that in the two control groups （P 〈 0.05）; on the 28^th day, positive neurons of calbindin D28K nearly disappeared, and the amount was lower than that in the two control groups （P 〈 0.01）. In addition, on the 7^th day after 6-OHDA injection into corpus striatum, positive TH neurons decreased 24% in right SN, and there was significant difference from that in control groups; on the 14^th, 21^st and 28^th days, positive TH neurons decreased 37%, 46% and 64%, respectively. ③ Western blot results： On the 14＇h day after 6-OHDA injection into corpus striatum, expression of calbindin D28K in right SN was higher in experimental group than that in both control groups （P 〈 0.05）; however, on the 28^th day, the expression was lower than that in the two control groups （P 〈 0.01 ）. CONCLUSION ： During degeneration and death of dopaminergic neurons, CB expression in SN pars compacta increases firstly and decreased gradually.展开更多
No-carrier-added 6-[^18F] fluoro-L-DOPA(6-FDOPA) was synthesized via a multistep procedure from a commercial available precursor,6-nitroveratraldehyde,The total synthesis time was 75min,with a radiochemical yield of (...No-carrier-added 6-[^18F] fluoro-L-DOPA(6-FDOPA) was synthesized via a multistep procedure from a commercial available precursor,6-nitroveratraldehyde,The total synthesis time was 75min,with a radiochemical yield of (10±3)%,high radiochemical purity(>99%) and high enantiomeric purity(>95%).The biodistributions of 6-FDOPA in normal and unilateral PD model rats were measured.The results from normal rats showed the expected high concentration of radioactivity in striatum and low distrbutions in cerebrum,cortex and cerebellum.The ration of the radioactivity in striatum to cerebellum reached a peak value(5.9) at 60 min.In unilateral PD model rate.whose substania nigra of the right side had been damaged by pre-treated with 6-OHDA,the radioactive concentration in striatum of the damaged side was significantly lower than that of the undamaged side or that of both sides in striatum of control groups.展开更多
Background:Adenoid hypertrophy(AH)is a common pediatric disease that signifi-cantly impacts the growth and quality of life of children.However,there is no replica-ble and valid model for AH.Methods:An AH rat model was...Background:Adenoid hypertrophy(AH)is a common pediatric disease that signifi-cantly impacts the growth and quality of life of children.However,there is no replica-ble and valid model for AH.Methods:An AH rat model was developed via comprehensive allergic sensitization,chronic inflammation induction,and chronic intermittent hypoxia(CIH).The modeling process involved three steps:female Sprague-Dawley rats(aged 4-5 weeks)were used for modeling.Allergen sensitization was induced via intraperitoneal administra-tion and intranasal provocation using ovalbumin(OVA);chronic nasal inflammation was induced through intranasal lipopolysaccharide(LPS)administration for sustained nasal irritation;CIH akin to obstructive sleep apnea/hypopnea syndrome was induced using an animal hypoxia chamber.Postmodel establishment,behaviors,and histologi-cal changes in nasopharynx-associated lymphoid tissue(NALT)and nasal mucosa were assessed.Arterial blood gas analysis and quantification of serum and tissue levels of(interleukin)IL-4 and IL-13,OVA-specific immunoglobulin E(sIgE),eosinophil cationic protein(ECP),tumor necrosis factor(TNF-α),IL-17,and transforming growth factor(TGF)-βwere conducted for assessment.The treatment group received a combination of mometasone furoate and montelukast sodium for a week and then was evaluated.Results:Rats exhibited notable nasal symptoms and hypoxia after modeling.Histopathological analysis revealed NALT follicle hypertrophy and nasal mucosa in-flammatory cell infiltration.Elevated IL-4,IL-13,IL-17,OVA-sIgE,ECP,and TNF-αlev-els and reduced TGF-βlevels were observed in the serum and tissue of model-group rats.After a week of treatment,the treatment group exhibited symptom and inflam-matory factor improvement.Conclusion:The model effectively simulates AH symptoms and pathological changes.But it should be further validated for genetic,immunological,and hormonal back-grounds in the currently used and other strains and species.展开更多
Frozen shoulder(FS),also known as adhesive capsulitis,is a condition that causes contraction and stiffness of the shoulder joint capsule.The main symptoms are per-sistent shoulder pain and a limited range of motion in...Frozen shoulder(FS),also known as adhesive capsulitis,is a condition that causes contraction and stiffness of the shoulder joint capsule.The main symptoms are per-sistent shoulder pain and a limited range of motion in all directions.These symp-toms and poor prognosis affect people's physical health and quality of life.Currently,the specific mechanisms of FS remain unclear,and there is variability in treatment methods and their efficacy.Additionally,the early symptoms of FS are difficult to distinguish from those of other shoulder diseases,complicating early diagnosis and treatment.Therefore,it is necessary to develop and utilize animal models to under-stand the pathogenesis of FS and to explore treatment strategies,providing insights into the prevention and treatment of human FS.This paper reviews the rat models available for FS research,including external immobilization models,surgical internal immobilization models,injection modeling models,and endocrine modeling models.It introduces the basic procedures for these models and compares and analyzes the advantages,disadvantages,and applicability of each modeling method.Finally,our paper summarizes the common methods for evaluating FS rat models.展开更多
The COVID-19 pandemic posed a challenge for clinical management of a new lung disease that was characterized by inflammation,endothelial cell dysfunction,and thrombosis,which occur after the replication phase of infec...The COVID-19 pandemic posed a challenge for clinical management of a new lung disease that was characterized by inflammation,endothelial cell dysfunction,and thrombosis,which occur after the replication phase of infection of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).There are many laboratory models of active SARS-CoV-2 infection in mice,reflecting an acute lung injury in an otherwise healthy animal,but there is a lack of accurate animal models of the postviral inflammatory phase of the COVID-19 lung reflecting severe disease.The monocrotaline(MCT)-treated rat is a widely used laboratory model of pulmonary hypertension(PH).Not often discussed,however,are the observed changes in inflammation,edema,fibrosis,and microthrombosis in the lung prior to PH.At the cellular level,there is loss of pneumocytes and endotheliopathy,and at the molecular level the MCT rat lung is characterized by a proinflammatory cytokine profile,namely elevated interleukin 6,transforming growth factorβand tumor necrosis factor,M1 macrophage phenotype,and dysregulation of the angiotensin converting enzyme(ACE)/ACE2 balance.The systems-level pathophysiology of the MCT-treated rat includes progressive cardiopulmonary dysfunction.The MCT-treated rat clearly differs from the COVID-19 lung in terms of the triggers for pathology,but there are many parallels apparent in both the MCT-treated rat and the COVID-19 lung.The MCT-treated rat lung as a model of the COVID-19 lung may provide an in-depth understanding of the factors that drive the lung to more severe pathology,treatments that benefit lung recovery,or the factors that prove a useful research platform for future emerging respiratory threats of similar pathology.展开更多
This review focuses on rat models for studying the short-term and long-term effects of mild and severe hypoglycemia.We explored the physiological mechanisms to understand the consequences of hypoglycemia in rat experi...This review focuses on rat models for studying the short-term and long-term effects of mild and severe hypoglycemia.We explored the physiological mechanisms to understand the consequences of hypoglycemia in rat experimental models.This study aims to investigate the therapeutic potential of phytotherapeutic agents and their efficacy in mitigating the adverse effects of hypoglycemia.Insights from our planned research will be beneficial in improving quality of life for individuals at risk of episodes of low blood sugar.Optimizing hypoglycemic rat models for research requires selecting a suitable experimental model that will be susceptible to hypoglycemia induction,effective monitoring of blood glucose levels,and maintaining a high survival rate throughout the required experimental duration.展开更多
Chronic pain after spine surgery(CPSS)is a complex disorder characterized by multifactorial pathogenesis that occurs in 8%–40%of patients undergoing lumbar spine surgery.We aimed to develop a rat model that mimics cl...Chronic pain after spine surgery(CPSS)is a complex disorder characterized by multifactorial pathogenesis that occurs in 8%–40%of patients undergoing lumbar spine surgery.We aimed to develop a rat model that mimics clinical CPSS conditions by taking two sequential surgical procedures.Step 1:A plastic rod was inserted into the left L5 intervertebral foramen to produce a steady compression on the dorsal root ganglion(DRG)and the spinal nerve,a common cause of low back pain(LBP).Step 2:The rod was removed after 7 days when rats exhibited mechanical and heat hypersensitivity in the ipsilateral hindpaw,followed by a full L5 laminectomy to mimic spine decompression surgery in LBP patients.The retention of the rod induced a prolonged LBP-like behavior but was quickly resolved after rod removal without laminectomy.However,rats that received laminectomy after rod removal developed heightened mechanical and heat sensitivity in the hindpaw,impaired gait,and reduced spontaneous exploration activity,indicating CPSS.Patch clamp recording revealed a significant augmentation in the intrinsic excitability of smalldiameter DRG neurons in CPSS rats.Administration of Dermorphin[D-Arg2,Lys4](1–4)amide(DALDA,5mg/kg,i.p.),a peripherally acting mu-opioid receptor(MOR)-preferred agonist,attenuated pain hypersensitivity,capsaicin-induced[Ca^(2+)]i rising and the increased intrinsic excitability of DRG neurons from CPSS rats.Our findings suggest that this new model,which mirrors the nature of CPSS developed in patients,may be useful for future studies of the underlying mechanisms.展开更多
[Objectives]To investigate the effect of extract A from Blumea megacephala(Randeria)Chang et Tseng on the hemostasis of postpartum uterine hemorrhage in early pregnancy rats.[Methods]12 mg/kg of mifepristone and 120μ...[Objectives]To investigate the effect of extract A from Blumea megacephala(Randeria)Chang et Tseng on the hemostasis of postpartum uterine hemorrhage in early pregnancy rats.[Methods]12 mg/kg of mifepristone and 120μg/kg of misoprostol were used to establish the uterine bleeding model of early pregnancy rats,and the effects of the drugs on the amount of uterine bleeding,the contents of angiotensin II(Ang-II)and prostaglandin E 2(PGE 2)in serum,the four factors of coagulation,platelet adhesion,platelet aggregation and platelet number were investigated.[Results]Extract A can shorten prothrombin time(PT)and activated partial thromboplastin time(APTT)in rats.It can reduce the amount of uterine bleeding in the model,reduce the contents of PGE 2 and Ang-II,reduce APTT and PT,increase the content of fibrinogen FIB,enhance platelet adhesion,enhance platelet aggregation and increase the number of platelets.[Conclusions]Extract A has obvious hemostatic effect on uterine bleeding model of early pregnancy rats.It may play a hemostatic role by affecting vasoconstriction-dilation,coagulation factors in the blood s internal and external coagulation system,platelet adhesion and aggregation,increasing FIB content,increasing platelet number,affecting uterine bleeding,etc.,showing the characteristics of multiple pathways and multiple targets.展开更多
The postpartum period is when a host of changes occur at molecular, cellular, physiological and behavioral levels to prepare female humans for the challenge of maternity. Alteration or prevention of these normal adapt...The postpartum period is when a host of changes occur at molecular, cellular, physiological and behavioral levels to prepare female humans for the challenge of maternity. Alteration or prevention of these normal adaptions is thought to contribute to disruptions of emotion regulation, motivation and cognitive abilities that underlie postpartum mental disorders, such as postpartum depression. Despite the high incidence of this disorder, and the detrimental consequences for both mother and child, its etiology and related neurobiological mechanisms remain poorly understood, partially due to the lack of appropriate animal models. In recent decades, there have been a number of attempts to model postpartum depression disorder in rats. In the present review, we first describe clinical symptoms of postpartum depression and discuss known risk factors, including both genetic and environmental factors. Thereafter, we discuss various rat models that have been developed to capture various aspects of this disorder and knowledge gained from such attempts. In doing so, we focus on the theories behind each attempt and the methods used to achieve their goals. Finally, we point out several understudied areas in this field and make suggestions for future directions.展开更多
AIM： To evaluate serum TIMP-1 level and the correlation between TIMP-1 expression and liver fibrosis in immuneinduced and CCL4-induced liver fibrosis models in rats. METHODS： Immune-induced and CCL4-induced liver fi...AIM： To evaluate serum TIMP-1 level and the correlation between TIMP-1 expression and liver fibrosis in immuneinduced and CCL4-induced liver fibrosis models in rats. METHODS： Immune-induced and CCL4-induced liver fibrosis models were established by dexamethasone （0.01 mg） and CCL4 respectively. Serum TIMP-1 level was detected with ELISA, while histopathological grade of liver biopsy was evaluated. Spearman rankcorrelation test was used to analyse the difference of the correlation between the TIMP-1 expression and hepatic fibrosis in the two fibrosis models. Furthermore,in situ hybridization was used to determine the expression difference of TIMP-1 mRNA in the two models. RESULTS： Positive correlation existed between serum TIMP-1 level of immune induced group and the histopathological stages of fibrosis liver of corresponding rats （Spearman rank-correlation test, rs = 0.812, P 0.05）, and the positive in situ hybridization signal of TIMP-1 mRNA was strong. In CCL4-induced liver fibrosis model, the correlation between the serum TIMP-1 level and the severity of hepatic fibrosis was not statistically significant（Spearman rank-correlation test, rs = 0.229, P 〉 0.05）. And compared with immune-induced model, the positivein situ hybridization signal of TIMP-1 mRNA was weaker, while the expression variation was higher in hepatic fibrosis of the same severity. CONCLUSION： The correlations between TIMP-1 expression and liver fibrosis in two rat liver fibrosis models are different. In immune-induced model, serum TIMP-1 level could reflect the severity of liver fibrosis, while in CCL4-induced model, the correlation between the serum TIMP-1 level and the severity of hepatic fibrosis was not statistically significant.展开更多
AIM:To develop a reliable,reproducible rat model of retinal vein occlusion(RVO)with a novel photosensitizer(erythrosin B)and study the cellular responses in the retina.METHODS:Central and branch RVOs were created in a...AIM:To develop a reliable,reproducible rat model of retinal vein occlusion(RVO)with a novel photosensitizer(erythrosin B)and study the cellular responses in the retina.METHODS:Central and branch RVOs were created in adult male rats via photochemically-induced ischemia.Retinal changes were monitored via color fundus photography and fluorescein angiography at 1 and 3h,and 1,4,7,14,and 21d after irradiation.Tissue slices were evaluated histopathologically.Retinal ganglion cell survival at different times after RVO induction was quantified by nuclear density count.Retinal thickness was also observed.RESULTS:For all rats in both the central and branch RVO groups,blood flow ceased immediately after laser irradiation and retinal edema was evident at one hour.The retinal detachment rate was 100%at 3h and developed into bullous retinal detachment within 24h.Retinal hemorrhages were not observed until 24h.Clearance of the occluded veins at 7d was observed by fluorescein angiography.Disease manifestation in the central RVO eyes was more severe than in the branch RVO group.A remarkable reduction in the ganglion cell count and retinal thickness was observed in the central RVO group by 21d,whereas moderate changes occurred in the branch RVO group.CONCLUSION:Rat RVO created by photochemicallyinduced ischemia using erythrosin B is a reproducible and reliable animal model for mimicking the key features of human RVO.However,considering the 100%rate ofretinal detachment,this animal model is more suitable for studying RVO with chronic retinal detachment.展开更多
AIM:To investigate the key factors in developing the trinitrobenzene sulfonic acid(TNBS)-induced postinflammatory irritable bowel syndrome(PI-IBS)model in rats. METHODS:TNBS was administered to rats at the following c...AIM:To investigate the key factors in developing the trinitrobenzene sulfonic acid(TNBS)-induced postinflammatory irritable bowel syndrome(PI-IBS)model in rats. METHODS:TNBS was administered to rats at the following conditions:(1)with different doses(20,10,5 mg/0.8 mL per rat);(2)with same dose in different concentrations(20 mg/rat,25,50 mg/mL);(3)in different ethanol percentage(25%,50%);and(4)at depth either 4 cm or 8 cm from anus.At 5 d and 4 wk after TNBS administration,inflammation severity and inflammation resolution were evaluated.At 4 and 8 wk after TNBS application,visceral hyperalgesia and enterochromaffin(EC)cell hyperplasia were assayed by abdominal withdrawal reflex test,silver staining and capillary electrophoresis. RESULTS:Our results showed that:(1)TNBS induced dose-dependent acute inflammation and inflammation resolution.At 5 d post TNBS,the pathological score and myeloperoxidase(MPO)activity in all TNBS treated rats were significantly elevated compared to that of the control(9.48±1.86,8.18±0.67,5.78± 0.77 vs 0,and 3.55±1.11,1.80±0.82,0.97±0.08 unit/mg vs 0.14±0.01 unit/mg,P<0.05).At 4 wk post TNBS,the pathological score in high and median dose TNBS-treated rats were still significantly higher than that of the control(1.52±0.38 and 0.80±0.35 vs 0,P<0.05);(2)Intracolonic TNBS administration position affected the persistence of visceral hyperalgesia.At 4 wk post TNBS,abdominal withdrawal reflex (AWR)threshold pressure in all TNBS-treated groups were decreased compared to that of the control(21.52 ±1.73 and 27.10±1.94 mmHg vs 34.44±1.89 mmHg,P<0.05).At 8 wk post TNBS,AWR threshold pressure in 8 cm administration group was still significantly decreased(23.33±1.33 mmHg vs 36.79±2.29 mmHg,P<0.05);(3)Ethanol percentage affected the TNBS-induced inflammation severity and visceral hyperalgesia.In TNBS-25%ethanol-treated group,the pathological score and MPO activity were significantly lowered compared to that of the TNBS-50%ethanoltreated group,while AWR threshold pressure were significantly elevated(36.33±0.61 mmHg vs 23.33±1.33 mmHg,P<0.05);and(4)TNBS(5 mg/0.8 mL per rat, in 50%ethanol,8 cm from anus)-treated rats recovered completely from the inflammation with acquired visceral hyperalgesia and EC cell hyperplasia at 4 wk after TNBS administration.CONCLUSION:TNBS dosage,concentration,intraco-lonic administration position,and ethanol percentage play important roles in developing visceral hyperalgesia and EC cell hyperplasia of TNBS-induced PI-IBS rats.展开更多
AIM To establish a rat model of anxiety-like gastric hyper-sensitivity(GHS) of functional dyspepsia(FD) induced by novel sequential stress.METHODS Animal pups were divided into two groups from postnatal day 2: control...AIM To establish a rat model of anxiety-like gastric hyper-sensitivity(GHS) of functional dyspepsia(FD) induced by novel sequential stress.METHODS Animal pups were divided into two groups from postnatal day 2: controls and the sequential-stress-treated. The sequential-stress-treated group received maternal separation and acute gastric irritation early in life and restraint stress in adulthood; controls were reared undisturbed with their mothers. Rats in both groups were followed to adulthood(8 wk) at which point the anxietylike behaviors and visceromotor responses to gastric distention(20-100 mm Hg) and gastric emptying were tested. Meanwhile, alterations in several anxiety-related brain-stomach modulators including 5-hydroxytryptamine(5-HT), γ-aminobutyric acid(GABA), brain-derived neurotrophic factor(BDNF) and nesfatin-1 in the rat hippocampus, plasma and gastric fundus and the 5-HT1 A receptor(5-HT1 AR) in the hippocampal CA1 subfield and the mucosa of the gastric fundus were examined.RESULTS Sequential-stress-treated rats simultaneously demonstrated anxiety-like behaviors and GHS in dose-dependent manner compared with the control group. Although rats in both groups consumed similar amount of solid food, the rate of gastric emptying was lower in the sequentialstress-treated rats than in the control group. Sequential stress significantly decreased the levels of 5-HT(51.91 ± 1.88 vs 104.21 ± 2.88, P < 0.01), GABA(2.38 ± 0.16 vs 5.01 ± 0.13, P < 0.01) and BDNF(304.40 ± 10.16 vs 698.17 ± 27.91, P < 0.01) in the hippocampus but increased the content of nesfatin-1(1961.38 ± 56.89 vs 1007.50 ± 33.05, P < 0.01) in the same site; significantly decreased the levels of 5-HT(47.82 ± 2.29 vs 89.45 ± 2.61, P < 0.01) and BDNF(257.05 ± 12.89 vs 536.71 ± 20.73, P < 0.01) in the plasma but increased the content of nesfatin-1 in it(1391.75 ± 42.77 vs 737.88 ± 33.15, P < 0.01); significantly decreased the levels of 5-HT(41.15 ± 1.81 vs 89.17 ± 2.31, P < 0.01) and BDNF(226.49 ± 12.10 vs 551.36 ± 16.47, P < 0.01) in the gastric fundus but increased the content of nesfatin-1 in the same site(1534.75 ± 38.52 vs 819.63 ± 38.04, P < 0.01). The expressions of 5-HT1 AR in the hippocampal CA1 subfield and the mucosa of the gastric fundus were down-regulated measured by IHC(Optical Density value: Hippocampus 15253.50 ± 760.35 vs 21149.75 ± 834.13; gastric fundus 15865.25 ± 521.24 vs 23865.75 ± 1868.60; P < 0.05, respectively) and WB(0.38 ± 0.01 vs 0.57 ± 0.03, P < 0.01)(n = 8 in each group). CONCLUSION Sequential stress could induce a potential rat model of anxiety-like GHS of FD, which could be used to research the mechanisms of this intractable disease.展开更多
BACKGROUND： Functional imaging such as CT perfusion can detect morphological and hemodynamic changes in he- patocellular carcinoma （HCC）. Pre-carcinoma and early HCC nodules are difficult to differentiate by observ...BACKGROUND： Functional imaging such as CT perfusion can detect morphological and hemodynamic changes in he- patocellular carcinoma （HCC）. Pre-carcinoma and early HCC nodules are difficult to differentiate by observing only their hemodynamics changes. The present study aimed to investi- gate hemodynamic parameters and evaluate their differential diagnostic cut-off between pre-carcinoma and early HCC nodules using CT perfusion and receiver operating characteristic （ROC） curves. METHODS： Male Wistar rats were randomly divided into control （n=20） and experimental （n=70） groups. Diethylnitrosamine （DEN） was used to induce pre-carcinoma and early HCC nodules in the experimental group. Perfusion scanning was carried out on all survival rats discontinuously from 8 to 16 weeks. Hepatic portal perfusion （HPP）, hepatic arterial fraction （HAF）, hepatic arterial perfusion （HAP）, hepatic blood volume （HBV）, hepatic blood flow （HBF）, mean transit time （MTT） and permeability of capillary vessel surface （PS） data were provided by mathematical deconvolution model. The perfusion parameters were compared among the three groups of rats （control, pre-carcinoma and early HCC groups） using the Kruskal-Wallis test and analyzed with ROC curves. Histological examination of the liver tissues with hematoxylin and eosin staining was performed after CT scan.RESULTS： For HPP, HAF, HBV, HBF and MTT, there were significant differences among the three groups （P〈0.05）. HAF had the highest areas under the ROC curves： 0.80 （control vs pre-carcinoma groups） and 0.95 （control vs early HCC groups） with corresponding optimal cut-offs of 0.37 and 0.42, respectively. The areas under the ROC curves for HPP was 0.79 （control vs pre-carcinoma groups） and 0.92 （control vs early HCC groups） with corresponding optimal cut-offs of 136.60 mL/min/100 mg and 108.47 mL/min/100 mg, respectively. CONCLUSIONS： CT perfusion combined with ROC curve analysis is a new diagnosis model for distinguishing between pre-carcinoma and early HCC nodules. HAF and HPP are the ideal reference indices.展开更多
INTRODUCTIONIn recent years,there have been many reports aboutanimal model to investigate drugs for inflammatorybowel diseases (IBD).The experimental animalmodel often used is acetic acid-induced damage ofcolonic musc...INTRODUCTIONIn recent years,there have been many reports aboutanimal model to investigate drugs for inflammatorybowel diseases (IBD).The experimental animalmodel often used is acetic acid-induced damage ofcolonic muscosa.In the present study,this animalmodel was investigated by administering variousconcentrations of TNBS.展开更多
AIM： To evaluate the neuroprotective effect of rosuvastatin, in a rat experimental glaucoma model. METHODS： Ocular hypertension was induced in right eyes of Long-Evans rats （n=30） by cauterization of three episcle...AIM： To evaluate the neuroprotective effect of rosuvastatin, in a rat experimental glaucoma model. METHODS： Ocular hypertension was induced in right eyes of Long-Evans rats （n=30） by cauterization of three episcleral veins. Left eyes were defined as controls. Rats were divided into five groups： oral rosuvastatin, intravitreal rosuvastatin, oral ＋intravitreal rosuvastatin, intravitreal sham and glaucoma without intervention. Rats were sacrificed at day 14. Retinal ganglion cell （RGC） number was assessed by histopathological analysis. Terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling （TUNEL） staining and the expression of glial fibrillary acidic protein （GFAP） in RGC layer was also examined. RESULTS： A significant intraocular pressure （lOP） elevation was seen （P=0.002）. Elevated lOP resulted in a significant decrease in number of RGCs in group 5 （70.33 ±8.2 cells/mm2） when compared with controls （92.50 ±13.72 cells/mm2; P=0.03）. The RGC number in group 1 （92.4±7.3 cells/mm2） was significantly higher than group 5 （ρ=0.03）. The numbers of RGC in groups 2, 3 （57.3±8.2 cells/mm2, 60.5±12.9 cells/mm2） were comparable with that of group 5 （ρ=0.18 and P=0.31）. The apoptosis rates with TUNEL staining were also parallel to RGC number. Animals with experimentally induced glaucoma showed an increase in retinal GFAP immunoreacUvity. CONCLUSION： Decrease in RGC loss and apoptosis suggest the neuroprotective potential of oral rosuvastatin treatment in a rat model of ocular hypertension. Howeverintravitreal rosuvastatin showed a contrary effect and further studies are required.展开更多
基金Supported by National Natural Science Foundation of China:81173327/H2718
文摘Objective To comparatively observe the effect of electroacupuncture at digestive system-related lower he-sea points on the expressions of serum interleukin-1β（IL-1 β）, tumor necrosis factor-α（TNF-α） of colon tissues and high mobility group box 1 protein（HMGB 1） of ulcerative colitis（UC） model rats, and to explore whether there is relative specificity of electroacupuncture at Shàngjùxū（上巨虚 ST 37）, one of lower he-sea points of large intestine, in treatment of bowel diseases. Method A total of 60 SD rats were randomly divided into control group, model group, ST 37 group, Zúsānl？（足三里 ST 36） group, Xiàjùxū（下巨虚 ST 39） group and Yánglíngquán（阳陵泉 GB 34） group. There were ten rats in each group; five were males, and five were females. UC models were established by clysis with 2, 4, 6-trinitrobenzene sulfonic acid/alcohol solution. After modeling, treatment was conducted for ten days, specimens were collected, colonic ulcers and inflammation were inspected visually and scored. The content of serum IL-1β and the expressions of TNF-α and HMGB 1 in colon were detected through ELISA. Results 1 Compared with control group, the scores of colonic ulcers and inflammation, the content of serum IL-1β and the expressions of TNF-α（except ST 37 group） and HMGB 1 were all higher（P〈0.05, P〈0.01）; 2 compared with model group, the scores of colonic ulcers in ST 36 group and ST 37 group were lower obviously（P〈0.05, P〈0.01）; the expressions of IL-1β, TNF-α and HMGB 1 in the four treatment groups were lower obviously（P〈0.01）; 3 compared with ST 37 group, the expressions of IL-1β, TNF-α and HMGB 1 in other three treatment groups were higher obviously（P〈0.05, P〈0.01）; and the scores of colonic ulcers in ST 39 group and GB 34 group were higher obviously（P〈0.05）. Conclusion 1 The score of colonic ulcers can be reduced through electroacupuncture at ST 37, ST 36, ST 39 and GB 34, which can also reduce the content of serum IL-1β and the expressions of TNF-α and HMGB 1, and effectively inhibit inflammatory response of colon caused by UC; 2 the effect trend of the four acupoints in treatment of UC is： ST 37ST 36ST 39GB 34, and electroacupuncture at ST 37 has the best effect with relative specificity.
基金supported by the National Natural Science Foundation of China(grant No.81971380 and No.82301822).
文摘Peyronie’s disease(PD)is a disorder characterized by fibrous plaque formation in the penile tissue that leads to curvature and complications in advanced stages.In this study,we aimed to compare four injectable induction agents for the establishment of a robust rat model of PD:transforming growth factor-β1(TGF-β1),fibrin,sodium tetradecyl sulfate(STS)combined with TGF-β1,and polidocanol(POL)combined with TGF-β1.The results showed that injection of TGF-β1 or fibrin into the tunica albuginea induced pathological endpoints without causing penile curvature.The STS+TGF-β1 combination resulted in both histological and morphological alterations,but with a high incidence of localized necrosis that led to animal death.The POL+TGF-β1 combination produced pathological changes and curvature comparable to STS+TGF-β1 and led to fewer complications.In conclusion,fibrin,STS+TGF-β1,and POL+TGF-β1 all induced PD with a certain degree of penile curvature and histological fibrosis in rats.The POL+TGF-β1 combination offered comparatively greater safety and clinical relevance and may have the greatest potential for PD research using model rats.
基金the Scientific andTechnological DevelopmentProgram of Qingdao City, No.No.05-1-NS-73
文摘BACKGROUND： Hypoxia inducible factor-1 alpha （HIF-1 （x） and erythropoietin（EPO）, possessing neuroprotective effect in the cerebral ischemia, might play an important role in the formation of cerebral ischemic tolerance （IT）. OBJECTIVE：To observe the neuroprotective effect of cerebral ischemic preconditioning（IPC） of rats, and the expression and mechanism of HIF-1α and target gene erythropoietin in the brain tissue following the formation of cerebral IT. DESIGN ： A randomized and controlled observation SETTING： Department of Neurology, the Affiliated Hospital of Medical College, Qingdao University MATERIALS： Totally 84 enrolled adult healthy male Wistar rats of clean grade, weighing 250 to 300 g, were provided by the Animal Experimental Department, Tongji Medical College of Huazhong University of Science and Technology. Ready-to-use SABC reagent kit and rabbit anti-rat HIF-1α monoclonal antibody were purchased from Boshide Bioengineering Co.Ltd （Wuhan）; Rabbit anti-rat EPO monoclonal antibody was purchased from Santa Cruz Company （USA）. METHODS： This experiment was carried out in the Department of Anatomy, Medical College, Qingdao University during March 2005 to March 2006. ① The 84 rats were divided into 3 groups by a lot： IPC group （n=40）, sham-operation group （n=40） and control group （n=4）. In the IPC group, middle cerebral artery was occluded for 2 hours respectively on the 1^st, 3^rd, 7^th, 14^th and 21^st days of the reperfusion following 10-minute preischemia was made using a modified middle cerebral artery second suture method from Zea-Longa. The rats were sacrificed 22 hours after reperfusion in the end of middle cerebral artery occlusion （MCAO）. That was to say, after 10-minute preischemia, suture was exited to the extemal carotid artery and embedded subcutaneously. Middle cerebral artery was occluded again to form the second reperfusion at the set time point after reperfusion. Twenty-two hours later, rats were sacrificed; In the sham-operation group,the preischemia was substituted by sham-operation（only common carotid artery and crotch were exposed, and MCAO by suture was omitted）, and the other procedures were the same as those in the IPC group. In the control group, rats were given sham-operation twice at an interval of one day, and they were sacrificed 24 hours after the second sham-operation. ② Brain tissue was taken from the rats in each group. Cerebral infarction area of each layer was measured with TTC staining, and total cerebral infarction volume （The total cerebral infarction area of each layerxinterspace ） was calculated. After brain tissue was stained by haematoxylin-esoin （HE）, the form of nerve cells was observed under an optical microscope, and the expressions of HIF-1α（and EPO protein in the brain tissue were detected with immunohistochemical method. MAIN OUTCOME MEASURES： ①Cerebral infarction volume;②form of nerve cell; ③ the expression of HIF-1α and EPO protein in the brain tissue. RESULTS：Totally 84 rats were enrolled in the experiment. The dead rats were randomly supplied during the experiment, and finally 84 rats entered the stage of result analysis. ① Detection of cerebral infarction volume of rats in each group： Cerebral infarction volume in the IPC group was significantly smaller than that in the sham-operation group on the 1^st, 3^rd and 7^th days after reperfusion respectively [（161.2±6.9） mm^3 vs （219.9±11.2） mm^3, （134.9±9.0） mm^3 vs （218.6±13.0） mm^3, （142.9±13.7） mm^3 vs （221.3±14.2） mm^3, t=-8.924, 10.587,7.947, P〈 0.01]. ② Observation of nerve cell form of brain tissue： HE staining showed that the ischemic degree, range and cerebral edema degree of IPC group were significantly milder than those of sham-operation group. ③ The expressions of HIF-1α and EPO protein in cerebral cortex and hippocampus ： The expression of HIF-1αof IPC group was significantly higher than that of sham-operation group on the 1^st, 3^rd and 7^th days after reperfusion respectively （125.93±3.79 vs 117.65±5.60, 140.63±4.64 vs 119.33±4.26, 131.15±2.74 vs 107.60±3.89, t=2.449, 6.763,9.899,P 〈 0.05-0.01）. The expression of EPO of IPC group was significantly higher than that of sham-operation group on the 3^rd and 7^th days after perfusion respectively （141.68±3.29 vs 126.33±4.51, 138.88±2.59 vs 125.58±6.18,t=5.499,3.970, P〈 0.05）. CONCLUSION ： ①IPC can protect the never cells in rat brain and the best time to onset of cerebral IT induced by IPC is 1 to 7 days after reperfusion. ② Neuroprotective effect of cerebral IT might be related to the expression of HIF-1α and its target gene EPO.
基金Scientific and Technological Project of State Ministry of Education, No. 204055 the Natural Science Foundation of Educational Bureau of Jiangsu Province, No. 02KJB310009
文摘BACKGROUND： Previous researches suggested that expression level of calbindin D28K mRNA decreased in substantia nigra （SN） of model rats with Parkinson disease （PD）, and this might be related to the decrease of anti-degeneration potentials of dopaminergic neurons. OBJECTIVE： To observe expression changes of calbindin D28K in SN dopaminergic neurons during their degeneration and death in midbrain of PD model rats. DESIGN： Completely randomized grouping design SETTING： Department of Neurobiology, Xuzhou Medical College MATERIALS＂ A total of 92 healthy male SD rats, with the age of 3 months, weighing 200-250 g, were selected from Experimental Animal Center of Xuzhou Medical College [certification： SCXK （su） 2003-0003]. Calbindin D28K（CB）, tyroxine hydroxylase （TH）, ABC kit, 6-hydroxydopamine （6-OHDA） and Nissl dyes were provided by Sigma Company, and sheep serum was provided by Beijing Zhongshan Company. METHODS： The experiment was carried out in the Neurobiological Center of Xuzhou Medical College from October 2003 to October 2004. ① With lot method, rats were divided into blank control group （n=28）, experimental control group （n=-28） and experimental group （n=36）. Rats in experimental group were injected with 6-OHDA at right corpus striatum for PD modeling; rats in experimental control group were injected with saline at the same site; rats in blank control group did not give any injections.② On the 7^th, 14^th, 21^st and 28^th days, SN segments on right midbrain from every 5 rats in experimental group were fixed, embedded with paraffin and cut into successively coronary pieces. Rats in other two groups were treated with the same methods and then stained with Nissl to show neuronal form. Meanwhile, CB and TH antibodies staining with immunohistochemistry were used to show CB containing dopaminergic neurons and dopaminergic neurons, and cells were calculated and observed under optic microscope. ③ On the 14^th and 28^th days, every 4 rats in experimental group and every 4 rats in control group were selected to obtain their brains and separate SN on the injured side. Western blot was used to detect expression of calbindin D28K, protein band was scanned with imaging equipment, and data were analyzed with LabWorks software. MAIN OUTCOME MEASURES：① On the 7^th, 14^th, 21^st and 28^th days, Nissl staining results of SN neurons and immunohistochemical staining results of CB and TH antibodies; ② On the 14^th and 28^th days, Western blot results of calbindin D28K in SN neurons, RESULTS; Among 92 rats, 2 rats in experimental group died after 1 day due to 6-OHDA injection and other 90 rats were involved in the final analysis. ①Nissl staining results： On the 7^th day of 6-OHDA injection, most neuronal somas on right SN pars compacta were shown as deep pycnosis or lysis breakage; on the 14^th and 21^st days, amount of neurons was decreased remarkably; on the 28^th day, most neurons in SN pars compacta disappeared. ② Results of immunohistochemical staining： Amount of positive neurons of calbindin D28K in right SN pars compacta was not changed on the 7^th day after 6-OHDA injection; on the 14^th day, the amount was higher in experimental group than that in both control groups （P 〈 0.01） and was decreased till the 21^st day, but it was still higher than that in the two control groups （P 〈 0.05）; on the 28^th day, positive neurons of calbindin D28K nearly disappeared, and the amount was lower than that in the two control groups （P 〈 0.01）. In addition, on the 7^th day after 6-OHDA injection into corpus striatum, positive TH neurons decreased 24% in right SN, and there was significant difference from that in control groups; on the 14^th, 21^st and 28^th days, positive TH neurons decreased 37%, 46% and 64%, respectively. ③ Western blot results： On the 14＇h day after 6-OHDA injection into corpus striatum, expression of calbindin D28K in right SN was higher in experimental group than that in both control groups （P 〈 0.05）; however, on the 28^th day, the expression was lower than that in the two control groups （P 〈 0.01 ）. CONCLUSION ： During degeneration and death of dopaminergic neurons, CB expression in SN pars compacta increases firstly and decreased gradually.
基金Supported by the National Nature Sciences Foundation(10075073)
文摘No-carrier-added 6-[^18F] fluoro-L-DOPA(6-FDOPA) was synthesized via a multistep procedure from a commercial available precursor,6-nitroveratraldehyde,The total synthesis time was 75min,with a radiochemical yield of (10±3)%,high radiochemical purity(>99%) and high enantiomeric purity(>95%).The biodistributions of 6-FDOPA in normal and unilateral PD model rats were measured.The results from normal rats showed the expected high concentration of radioactivity in striatum and low distrbutions in cerebrum,cortex and cerebellum.The ration of the radioactivity in striatum to cerebellum reached a peak value(5.9) at 60 min.In unilateral PD model rate.whose substania nigra of the right side had been damaged by pre-treated with 6-OHDA,the radioactive concentration in striatum of the damaged side was significantly lower than that of the undamaged side or that of both sides in striatum of control groups.
基金This work was financially supported by the National Natural Science Foundation of China(grant number:8217150152)the Clinical Science and Technology Innovation Project of Shanghai Shenkang Hospital Development Center(grant number:SHDC12021102)the Shanghai Three-Year Action Plan to Further Accelerate the Development of Traditional Chinese Medicine Inheritance and Innovation(grant number:ZY(2021-2023)-0209-05).
文摘Background:Adenoid hypertrophy(AH)is a common pediatric disease that signifi-cantly impacts the growth and quality of life of children.However,there is no replica-ble and valid model for AH.Methods:An AH rat model was developed via comprehensive allergic sensitization,chronic inflammation induction,and chronic intermittent hypoxia(CIH).The modeling process involved three steps:female Sprague-Dawley rats(aged 4-5 weeks)were used for modeling.Allergen sensitization was induced via intraperitoneal administra-tion and intranasal provocation using ovalbumin(OVA);chronic nasal inflammation was induced through intranasal lipopolysaccharide(LPS)administration for sustained nasal irritation;CIH akin to obstructive sleep apnea/hypopnea syndrome was induced using an animal hypoxia chamber.Postmodel establishment,behaviors,and histologi-cal changes in nasopharynx-associated lymphoid tissue(NALT)and nasal mucosa were assessed.Arterial blood gas analysis and quantification of serum and tissue levels of(interleukin)IL-4 and IL-13,OVA-specific immunoglobulin E(sIgE),eosinophil cationic protein(ECP),tumor necrosis factor(TNF-α),IL-17,and transforming growth factor(TGF)-βwere conducted for assessment.The treatment group received a combination of mometasone furoate and montelukast sodium for a week and then was evaluated.Results:Rats exhibited notable nasal symptoms and hypoxia after modeling.Histopathological analysis revealed NALT follicle hypertrophy and nasal mucosa in-flammatory cell infiltration.Elevated IL-4,IL-13,IL-17,OVA-sIgE,ECP,and TNF-αlev-els and reduced TGF-βlevels were observed in the serum and tissue of model-group rats.After a week of treatment,the treatment group exhibited symptom and inflam-matory factor improvement.Conclusion:The model effectively simulates AH symptoms and pathological changes.But it should be further validated for genetic,immunological,and hormonal back-grounds in the currently used and other strains and species.
基金National Key R&D Program of China,Grant/Award Number:2021YFC2502100,2023YFC3603404 and 2019YFA0111900The National Natural Science Foundation of China,Grant/Award Number:82072506,82272611 and 92268115+7 种基金The Hunan Provincial Science Fund for Distinguished Young Scholars,Grant/Award Number:2024JJ2089The Hunan Young Talents of Science and Technology,Grant/Award Number:2021RC3025The Provincial Clinical Medical Technology Innovation Project of Hunan,Grant/Award Number:2023SK2024 and 2020SK53709The Provincial Natural Science Foundation of Hunan,Grant/Award Number:2020JJ3060The National Natural Science Foundation of Hunan Province,Grant/Award Number:2023JJ30949The National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Grant/Award Number:2021KFJJ02 and 2021LNJJ05The Hunan Provincial Innovation Foundation for Postgraduate,Grant/Award Number:CX20230308 and CX20230312The Independent Exploration and Innovation Project for Postgraduate Students of Central South University,Grant/Award Number:2024ZZTS0163。
文摘Frozen shoulder(FS),also known as adhesive capsulitis,is a condition that causes contraction and stiffness of the shoulder joint capsule.The main symptoms are per-sistent shoulder pain and a limited range of motion in all directions.These symp-toms and poor prognosis affect people's physical health and quality of life.Currently,the specific mechanisms of FS remain unclear,and there is variability in treatment methods and their efficacy.Additionally,the early symptoms of FS are difficult to distinguish from those of other shoulder diseases,complicating early diagnosis and treatment.Therefore,it is necessary to develop and utilize animal models to under-stand the pathogenesis of FS and to explore treatment strategies,providing insights into the prevention and treatment of human FS.This paper reviews the rat models available for FS research,including external immobilization models,surgical internal immobilization models,injection modeling models,and endocrine modeling models.It introduces the basic procedures for these models and compares and analyzes the advantages,disadvantages,and applicability of each modeling method.Finally,our paper summarizes the common methods for evaluating FS rat models.
基金College of Medicine and Public Health,MD,Advanced Studies ProgramAustralian National Health and Medical Research Council(NHMRC),Grant/Award Number:GNT2003683。
文摘The COVID-19 pandemic posed a challenge for clinical management of a new lung disease that was characterized by inflammation,endothelial cell dysfunction,and thrombosis,which occur after the replication phase of infection of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).There are many laboratory models of active SARS-CoV-2 infection in mice,reflecting an acute lung injury in an otherwise healthy animal,but there is a lack of accurate animal models of the postviral inflammatory phase of the COVID-19 lung reflecting severe disease.The monocrotaline(MCT)-treated rat is a widely used laboratory model of pulmonary hypertension(PH).Not often discussed,however,are the observed changes in inflammation,edema,fibrosis,and microthrombosis in the lung prior to PH.At the cellular level,there is loss of pneumocytes and endotheliopathy,and at the molecular level the MCT rat lung is characterized by a proinflammatory cytokine profile,namely elevated interleukin 6,transforming growth factorβand tumor necrosis factor,M1 macrophage phenotype,and dysregulation of the angiotensin converting enzyme(ACE)/ACE2 balance.The systems-level pathophysiology of the MCT-treated rat includes progressive cardiopulmonary dysfunction.The MCT-treated rat clearly differs from the COVID-19 lung in terms of the triggers for pathology,but there are many parallels apparent in both the MCT-treated rat and the COVID-19 lung.The MCT-treated rat lung as a model of the COVID-19 lung may provide an in-depth understanding of the factors that drive the lung to more severe pathology,treatments that benefit lung recovery,or the factors that prove a useful research platform for future emerging respiratory threats of similar pathology.
基金Correspondence:Christina Gertrude Yap,Jeffrey Cheah School of Medicine and Health Sciences,Monash University,Jalan Lagoon Selatan,Bandar Sunway,Subang Jaya 47500,Selangor,Malaysia.Email:christina.yap@monash.edu。
文摘This review focuses on rat models for studying the short-term and long-term effects of mild and severe hypoglycemia.We explored the physiological mechanisms to understand the consequences of hypoglycemia in rat experimental models.This study aims to investigate the therapeutic potential of phytotherapeutic agents and their efficacy in mitigating the adverse effects of hypoglycemia.Insights from our planned research will be beneficial in improving quality of life for individuals at risk of episodes of low blood sugar.Optimizing hypoglycemic rat models for research requires selecting a suitable experimental model that will be susceptible to hypoglycemia induction,effective monitoring of blood glucose levels,and maintaining a high survival rate throughout the required experimental duration.
基金supported by the Neurosurgery Pain Research Institute at Johns Hopkins University and by the Lehner Family Foundation.
文摘Chronic pain after spine surgery(CPSS)is a complex disorder characterized by multifactorial pathogenesis that occurs in 8%–40%of patients undergoing lumbar spine surgery.We aimed to develop a rat model that mimics clinical CPSS conditions by taking two sequential surgical procedures.Step 1:A plastic rod was inserted into the left L5 intervertebral foramen to produce a steady compression on the dorsal root ganglion(DRG)and the spinal nerve,a common cause of low back pain(LBP).Step 2:The rod was removed after 7 days when rats exhibited mechanical and heat hypersensitivity in the ipsilateral hindpaw,followed by a full L5 laminectomy to mimic spine decompression surgery in LBP patients.The retention of the rod induced a prolonged LBP-like behavior but was quickly resolved after rod removal without laminectomy.However,rats that received laminectomy after rod removal developed heightened mechanical and heat sensitivity in the hindpaw,impaired gait,and reduced spontaneous exploration activity,indicating CPSS.Patch clamp recording revealed a significant augmentation in the intrinsic excitability of smalldiameter DRG neurons in CPSS rats.Administration of Dermorphin[D-Arg2,Lys4](1–4)amide(DALDA,5mg/kg,i.p.),a peripherally acting mu-opioid receptor(MOR)-preferred agonist,attenuated pain hypersensitivity,capsaicin-induced[Ca^(2+)]i rising and the increased intrinsic excitability of DRG neurons from CPSS rats.Our findings suggest that this new model,which mirrors the nature of CPSS developed in patients,may be useful for future studies of the underlying mechanisms.
基金Supported by the University-level Project of Guangxi University of Chinese Medicine(2021ZD005).
文摘[Objectives]To investigate the effect of extract A from Blumea megacephala(Randeria)Chang et Tseng on the hemostasis of postpartum uterine hemorrhage in early pregnancy rats.[Methods]12 mg/kg of mifepristone and 120μg/kg of misoprostol were used to establish the uterine bleeding model of early pregnancy rats,and the effects of the drugs on the amount of uterine bleeding,the contents of angiotensin II(Ang-II)and prostaglandin E 2(PGE 2)in serum,the four factors of coagulation,platelet adhesion,platelet aggregation and platelet number were investigated.[Results]Extract A can shorten prothrombin time(PT)and activated partial thromboplastin time(APTT)in rats.It can reduce the amount of uterine bleeding in the model,reduce the contents of PGE 2 and Ang-II,reduce APTT and PT,increase the content of fibrinogen FIB,enhance platelet adhesion,enhance platelet aggregation and increase the number of platelets.[Conclusions]Extract A has obvious hemostatic effect on uterine bleeding model of early pregnancy rats.It may play a hemostatic role by affecting vasoconstriction-dilation,coagulation factors in the blood s internal and external coagulation system,platelet adhesion and aggregation,increasing FIB content,increasing platelet number,affecting uterine bleeding,etc.,showing the characteristics of multiple pathways and multiple targets.
基金Foundation items： The preparation of this review was partially supported by a grant from the National Institute of Mental Health （5R01 MH097718-02）, U.S.A.
文摘The postpartum period is when a host of changes occur at molecular, cellular, physiological and behavioral levels to prepare female humans for the challenge of maternity. Alteration or prevention of these normal adaptions is thought to contribute to disruptions of emotion regulation, motivation and cognitive abilities that underlie postpartum mental disorders, such as postpartum depression. Despite the high incidence of this disorder, and the detrimental consequences for both mother and child, its etiology and related neurobiological mechanisms remain poorly understood, partially due to the lack of appropriate animal models. In recent decades, there have been a number of attempts to model postpartum depression disorder in rats. In the present review, we first describe clinical symptoms of postpartum depression and discuss known risk factors, including both genetic and environmental factors. Thereafter, we discuss various rat models that have been developed to capture various aspects of this disorder and knowledge gained from such attempts. In doing so, we focus on the theories behind each attempt and the methods used to achieve their goals. Finally, we point out several understudied areas in this field and make suggestions for future directions.
基金Supported by the Postdoctoral Science Foundation of China, No.1999-10the Science and Technology Foundation of Shaanxi Province, China, No. 2003K10G63
文摘AIM： To evaluate serum TIMP-1 level and the correlation between TIMP-1 expression and liver fibrosis in immuneinduced and CCL4-induced liver fibrosis models in rats. METHODS： Immune-induced and CCL4-induced liver fibrosis models were established by dexamethasone （0.01 mg） and CCL4 respectively. Serum TIMP-1 level was detected with ELISA, while histopathological grade of liver biopsy was evaluated. Spearman rankcorrelation test was used to analyse the difference of the correlation between the TIMP-1 expression and hepatic fibrosis in the two fibrosis models. Furthermore,in situ hybridization was used to determine the expression difference of TIMP-1 mRNA in the two models. RESULTS： Positive correlation existed between serum TIMP-1 level of immune induced group and the histopathological stages of fibrosis liver of corresponding rats （Spearman rank-correlation test, rs = 0.812, P 0.05）, and the positive in situ hybridization signal of TIMP-1 mRNA was strong. In CCL4-induced liver fibrosis model, the correlation between the serum TIMP-1 level and the severity of hepatic fibrosis was not statistically significant（Spearman rank-correlation test, rs = 0.229, P 〉 0.05）. And compared with immune-induced model, the positivein situ hybridization signal of TIMP-1 mRNA was weaker, while the expression variation was higher in hepatic fibrosis of the same severity. CONCLUSION： The correlations between TIMP-1 expression and liver fibrosis in two rat liver fibrosis models are different. In immune-induced model, serum TIMP-1 level could reflect the severity of liver fibrosis, while in CCL4-induced model, the correlation between the serum TIMP-1 level and the severity of hepatic fibrosis was not statistically significant.
基金Supported by National Natural Science Foundation of China(No.81100681)
文摘AIM:To develop a reliable,reproducible rat model of retinal vein occlusion(RVO)with a novel photosensitizer(erythrosin B)and study the cellular responses in the retina.METHODS:Central and branch RVOs were created in adult male rats via photochemically-induced ischemia.Retinal changes were monitored via color fundus photography and fluorescein angiography at 1 and 3h,and 1,4,7,14,and 21d after irradiation.Tissue slices were evaluated histopathologically.Retinal ganglion cell survival at different times after RVO induction was quantified by nuclear density count.Retinal thickness was also observed.RESULTS:For all rats in both the central and branch RVO groups,blood flow ceased immediately after laser irradiation and retinal edema was evident at one hour.The retinal detachment rate was 100%at 3h and developed into bullous retinal detachment within 24h.Retinal hemorrhages were not observed until 24h.Clearance of the occluded veins at 7d was observed by fluorescein angiography.Disease manifestation in the central RVO eyes was more severe than in the branch RVO group.A remarkable reduction in the ganglion cell count and retinal thickness was observed in the central RVO group by 21d,whereas moderate changes occurred in the branch RVO group.CONCLUSION:Rat RVO created by photochemicallyinduced ischemia using erythrosin B is a reproducible and reliable animal model for mimicking the key features of human RVO.However,considering the 100%rate ofretinal detachment,this animal model is more suitable for studying RVO with chronic retinal detachment.
基金Supported by Hong Kong Jockey Club Institute of Chinese Medicine,No.JCICM-4-07
文摘AIM:To investigate the key factors in developing the trinitrobenzene sulfonic acid(TNBS)-induced postinflammatory irritable bowel syndrome(PI-IBS)model in rats. METHODS:TNBS was administered to rats at the following conditions:(1)with different doses(20,10,5 mg/0.8 mL per rat);(2)with same dose in different concentrations(20 mg/rat,25,50 mg/mL);(3)in different ethanol percentage(25%,50%);and(4)at depth either 4 cm or 8 cm from anus.At 5 d and 4 wk after TNBS administration,inflammation severity and inflammation resolution were evaluated.At 4 and 8 wk after TNBS application,visceral hyperalgesia and enterochromaffin(EC)cell hyperplasia were assayed by abdominal withdrawal reflex test,silver staining and capillary electrophoresis. RESULTS:Our results showed that:(1)TNBS induced dose-dependent acute inflammation and inflammation resolution.At 5 d post TNBS,the pathological score and myeloperoxidase(MPO)activity in all TNBS treated rats were significantly elevated compared to that of the control(9.48±1.86,8.18±0.67,5.78± 0.77 vs 0,and 3.55±1.11,1.80±0.82,0.97±0.08 unit/mg vs 0.14±0.01 unit/mg,P<0.05).At 4 wk post TNBS,the pathological score in high and median dose TNBS-treated rats were still significantly higher than that of the control(1.52±0.38 and 0.80±0.35 vs 0,P<0.05);(2)Intracolonic TNBS administration position affected the persistence of visceral hyperalgesia.At 4 wk post TNBS,abdominal withdrawal reflex (AWR)threshold pressure in all TNBS-treated groups were decreased compared to that of the control(21.52 ±1.73 and 27.10±1.94 mmHg vs 34.44±1.89 mmHg,P<0.05).At 8 wk post TNBS,AWR threshold pressure in 8 cm administration group was still significantly decreased(23.33±1.33 mmHg vs 36.79±2.29 mmHg,P<0.05);(3)Ethanol percentage affected the TNBS-induced inflammation severity and visceral hyperalgesia.In TNBS-25%ethanol-treated group,the pathological score and MPO activity were significantly lowered compared to that of the TNBS-50%ethanoltreated group,while AWR threshold pressure were significantly elevated(36.33±0.61 mmHg vs 23.33±1.33 mmHg,P<0.05);and(4)TNBS(5 mg/0.8 mL per rat, in 50%ethanol,8 cm from anus)-treated rats recovered completely from the inflammation with acquired visceral hyperalgesia and EC cell hyperplasia at 4 wk after TNBS administration.CONCLUSION:TNBS dosage,concentration,intraco-lonic administration position,and ethanol percentage play important roles in developing visceral hyperalgesia and EC cell hyperplasia of TNBS-induced PI-IBS rats.
文摘AIM To establish a rat model of anxiety-like gastric hyper-sensitivity(GHS) of functional dyspepsia(FD) induced by novel sequential stress.METHODS Animal pups were divided into two groups from postnatal day 2: controls and the sequential-stress-treated. The sequential-stress-treated group received maternal separation and acute gastric irritation early in life and restraint stress in adulthood; controls were reared undisturbed with their mothers. Rats in both groups were followed to adulthood(8 wk) at which point the anxietylike behaviors and visceromotor responses to gastric distention(20-100 mm Hg) and gastric emptying were tested. Meanwhile, alterations in several anxiety-related brain-stomach modulators including 5-hydroxytryptamine(5-HT), γ-aminobutyric acid(GABA), brain-derived neurotrophic factor(BDNF) and nesfatin-1 in the rat hippocampus, plasma and gastric fundus and the 5-HT1 A receptor(5-HT1 AR) in the hippocampal CA1 subfield and the mucosa of the gastric fundus were examined.RESULTS Sequential-stress-treated rats simultaneously demonstrated anxiety-like behaviors and GHS in dose-dependent manner compared with the control group. Although rats in both groups consumed similar amount of solid food, the rate of gastric emptying was lower in the sequentialstress-treated rats than in the control group. Sequential stress significantly decreased the levels of 5-HT(51.91 ± 1.88 vs 104.21 ± 2.88, P < 0.01), GABA(2.38 ± 0.16 vs 5.01 ± 0.13, P < 0.01) and BDNF(304.40 ± 10.16 vs 698.17 ± 27.91, P < 0.01) in the hippocampus but increased the content of nesfatin-1(1961.38 ± 56.89 vs 1007.50 ± 33.05, P < 0.01) in the same site; significantly decreased the levels of 5-HT(47.82 ± 2.29 vs 89.45 ± 2.61, P < 0.01) and BDNF(257.05 ± 12.89 vs 536.71 ± 20.73, P < 0.01) in the plasma but increased the content of nesfatin-1 in it(1391.75 ± 42.77 vs 737.88 ± 33.15, P < 0.01); significantly decreased the levels of 5-HT(41.15 ± 1.81 vs 89.17 ± 2.31, P < 0.01) and BDNF(226.49 ± 12.10 vs 551.36 ± 16.47, P < 0.01) in the gastric fundus but increased the content of nesfatin-1 in the same site(1534.75 ± 38.52 vs 819.63 ± 38.04, P < 0.01). The expressions of 5-HT1 AR in the hippocampal CA1 subfield and the mucosa of the gastric fundus were down-regulated measured by IHC(Optical Density value: Hippocampus 15253.50 ± 760.35 vs 21149.75 ± 834.13; gastric fundus 15865.25 ± 521.24 vs 23865.75 ± 1868.60; P < 0.05, respectively) and WB(0.38 ± 0.01 vs 0.57 ± 0.03, P < 0.01)(n = 8 in each group). CONCLUSION Sequential stress could induce a potential rat model of anxiety-like GHS of FD, which could be used to research the mechanisms of this intractable disease.
基金supported by grants from the National Natural Science Foundation of China(81301275,81471736 and 81671760)the National Science and Technology Pillar Program during the Twelfth Five-Year Plan Period(2015BAI01B09)Heilongjiang Province Foundation for Returness(LC2013C38)
文摘BACKGROUND： Functional imaging such as CT perfusion can detect morphological and hemodynamic changes in he- patocellular carcinoma （HCC）. Pre-carcinoma and early HCC nodules are difficult to differentiate by observing only their hemodynamics changes. The present study aimed to investi- gate hemodynamic parameters and evaluate their differential diagnostic cut-off between pre-carcinoma and early HCC nodules using CT perfusion and receiver operating characteristic （ROC） curves. METHODS： Male Wistar rats were randomly divided into control （n=20） and experimental （n=70） groups. Diethylnitrosamine （DEN） was used to induce pre-carcinoma and early HCC nodules in the experimental group. Perfusion scanning was carried out on all survival rats discontinuously from 8 to 16 weeks. Hepatic portal perfusion （HPP）, hepatic arterial fraction （HAF）, hepatic arterial perfusion （HAP）, hepatic blood volume （HBV）, hepatic blood flow （HBF）, mean transit time （MTT） and permeability of capillary vessel surface （PS） data were provided by mathematical deconvolution model. The perfusion parameters were compared among the three groups of rats （control, pre-carcinoma and early HCC groups） using the Kruskal-Wallis test and analyzed with ROC curves. Histological examination of the liver tissues with hematoxylin and eosin staining was performed after CT scan.RESULTS： For HPP, HAF, HBV, HBF and MTT, there were significant differences among the three groups （P〈0.05）. HAF had the highest areas under the ROC curves： 0.80 （control vs pre-carcinoma groups） and 0.95 （control vs early HCC groups） with corresponding optimal cut-offs of 0.37 and 0.42, respectively. The areas under the ROC curves for HPP was 0.79 （control vs pre-carcinoma groups） and 0.92 （control vs early HCC groups） with corresponding optimal cut-offs of 136.60 mL/min/100 mg and 108.47 mL/min/100 mg, respectively. CONCLUSIONS： CT perfusion combined with ROC curve analysis is a new diagnosis model for distinguishing between pre-carcinoma and early HCC nodules. HAF and HPP are the ideal reference indices.
文摘INTRODUCTIONIn recent years,there have been many reports aboutanimal model to investigate drugs for inflammatorybowel diseases (IBD).The experimental animalmodel often used is acetic acid-induced damage ofcolonic muscosa.In the present study,this animalmodel was investigated by administering variousconcentrations of TNBS.
基金Supported by Gazi University Research and Education Fund
文摘AIM： To evaluate the neuroprotective effect of rosuvastatin, in a rat experimental glaucoma model. METHODS： Ocular hypertension was induced in right eyes of Long-Evans rats （n=30） by cauterization of three episcleral veins. Left eyes were defined as controls. Rats were divided into five groups： oral rosuvastatin, intravitreal rosuvastatin, oral ＋intravitreal rosuvastatin, intravitreal sham and glaucoma without intervention. Rats were sacrificed at day 14. Retinal ganglion cell （RGC） number was assessed by histopathological analysis. Terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labeling （TUNEL） staining and the expression of glial fibrillary acidic protein （GFAP） in RGC layer was also examined. RESULTS： A significant intraocular pressure （lOP） elevation was seen （P=0.002）. Elevated lOP resulted in a significant decrease in number of RGCs in group 5 （70.33 ±8.2 cells/mm2） when compared with controls （92.50 ±13.72 cells/mm2; P=0.03）. The RGC number in group 1 （92.4±7.3 cells/mm2） was significantly higher than group 5 （ρ=0.03）. The numbers of RGC in groups 2, 3 （57.3±8.2 cells/mm2, 60.5±12.9 cells/mm2） were comparable with that of group 5 （ρ=0.18 and P=0.31）. The apoptosis rates with TUNEL staining were also parallel to RGC number. Animals with experimentally induced glaucoma showed an increase in retinal GFAP immunoreacUvity. CONCLUSION： Decrease in RGC loss and apoptosis suggest the neuroprotective potential of oral rosuvastatin treatment in a rat model of ocular hypertension. Howeverintravitreal rosuvastatin showed a contrary effect and further studies are required.
