Diabetes mellitus is a major public health concern. Finding a cure for the disease without its side-effects is the objective of modem medicine. The plant is a raw material for these studies. Zygophyllum gemini is a sp...Diabetes mellitus is a major public health concern. Finding a cure for the disease without its side-effects is the objective of modem medicine. The plant is a raw material for these studies. Zygophyllum gemini is a species widely used in Algeria to treat this disease. Our aim is to investigate the antidiabetic activity of aqueous extract and its fractions in induced diabetic Wistar rats by streptozotoein. The three drugs caused a decrease in blood sugar for 14 days. Butanolic fractions （BF） fraction gives significant results on blood glucose after seven days and significant regulating oral glucose tolerance. This preliminary study shows that Z. geslini is endowed with a remarkable antidiabetic activity and that further studies are needed.展开更多
Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ ...Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ on diabetic rats with ED and its potential mechanism viathe assessment of advanced glycosylation end products （AGEs）, autophagy, mTOR and the NO-cGMP pathway. Icarisid Ⅱ was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid Ⅱ group, rats were administered icarisid Ⅱ intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure （ICP/MAP）. AGE concentrations, nitric oxide synthase （NOS） activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 Iocalisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid Ⅱ increased ICP/MAP values, the smooth muscle cell （SMC） growth curve, S phase and SMC/collagen fibril （SMC/CF） proportions and decreased Beclin 1 （P〈0.05）. Icarisid Ⅱ significantly increased the proliferative index and p-p70S6K（Thr389） levels and decreased the numbers of autophagosomes and the levels of LC3-11 （P〈0.01）. Icarisid Ⅱ decreased AGE concentrations and increased cGMP concentration, NOS activity （P〈0.05） and cNOS levels （P〈0.01） in the diabetic ED group. Therefore, Icarisid Ⅱ constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.展开更多
The present study investigated the effect of transplanting endothelial progenitor cells （EPCs） transfected with the vascular endothelial growth factor gene （VEGF165） into the corpora cavernosa of rats with diabeti...The present study investigated the effect of transplanting endothelial progenitor cells （EPCs） transfected with the vascular endothelial growth factor gene （VEGF165） into the corpora cavernosa of rats with diabetic erectile dysfunction （ED）. A rat model of diabetic ED was constructed via intraperitoneal injection of streptozotocin. After streptozotocin treatment, pre-treated EPCs from each of three groups of rats were transplanted into their corpora cavernosa. Our results, following intracavernosal pressure （ICP） monitoring, showed that ICP increased significantly among rats in the trial group when compared to the results from rats in the blank-plasmid and control groups during basal conditions and electrical stimulation （P〈O.01 for both comparisons）. Histological examination revealed extensive neovascularisation in the corpora cavernosa of rats in the trial group. Fluorescence microscopy indicated that many of the transplanted EPCs in the trial group survived, differentiated into endothelial cells and integrated into the sites of neovascularisation. Based on the results of this study, we conclude that transplantation of VEGF165-transfected EPCs into the corpora cavernosa of rats with diabetic ED restores erectile function.展开更多
The high incidence of erectile dysfunction （ED） in diabetes highlights a need for effective treatment strategies. Resveratrol, an activator of silent information regulator 2-related enzymes 1 （sirtuinl, SIRT1）, ha...The high incidence of erectile dysfunction （ED） in diabetes highlights a need for effective treatment strategies. Resveratrol, an activator of silent information regulator 2-related enzymes 1 （sirtuinl, SIRT1）, has received attention for its valuable effects in cancer, neurodegenerative diseases, longevity and cardiovascular disease. To explore the effects of resveratrol in diabetes-induced ED, resveratrol was administered to rats with streptozocin （65 mg kg-1）-induced diabetes. Erectile function, cavernous structure, tissue protein expression of silent information regulator 2-related enzymes 1 （sirtuinl, SIRT1）, p53 and forkhead transcription factor 0 3a （FOXO3a）, superoxide dismutase （SOD） activity and malondialdehyde （MDA） levels in the corpora cavernosa were studied. We found that SIRT1 was expressed in cavernosal tissue, and it was downregulated in the corpora of diabetic rats. The administration of resveratrol upregulated the expression of SI RT1 and restored erectile function. In contrast, resveratrol downregulated the expression of p53 and FOXO3a, which regulate apoptosis and oxidative stress. Furthermore, the resveratrol-treated group showed an improvement in smooth muscle content, SOD activity and MDA levels when compared with the diabetic group. Therefore, the ability of resveratrol to improve diabetes-induced ED is likely related to its activation of SIRT1 expression, thus causing the suppression of apoptosis and resistance towards oxidative stress.展开更多
AIM： To investigate the effect of Tangweian Jianji （TWAJJ） on the biomechanical and morphometrical remodeling of the upper gastrointestinal tract in diabetic rats. METHODS： Diabetes was induced in 27 rats by in- j...AIM： To investigate the effect of Tangweian Jianji （TWAJJ） on the biomechanical and morphometrical remodeling of the upper gastrointestinal tract in diabetic rats. METHODS： Diabetes was induced in 27 rats by in- jecting streptozotocin （40 mg/kg body weight）, the animals were then divided into three groups （n = 9 in each group）, i.e., diabetic control （DM）; high dose （10 g/kg, T1） and low dose （5 g/kg, T2）. Another 10 rats acted as normal controls （Control）. TWAJJ was admin- istered by gavage once daily. Blood glucose and serum insulin levels were measured. Circumferential length, wall thickness and opening angle were measured from esophageal, duodenal, jejunal and ileal ring segments. The residual strain was calculated from the morpho- metric data. Step-wise distension was carried out on esophageal and jejunal segments. The obtained data on the length, diameter and pressure changes were then used to calculate the circumferential and longitu- dinal stresses and strains. Real-time reverse transcrip- tion polymerase chain reaction was used to detect the receptor of advanced glycation end-products （RAGE） mRNA level in jejunal tissues. RESULTS： At the end of the experiment, the blood glucose level was significantly higher and the serum insulin level was significantly lower in DM, T1 and T2 groups than in the control group （Glucose： 30.23 ± 0.41 mmol/L, 27.48 ± 0.27 mmol/L and 27.84 ± 0.29 mmol/ L vs 5.05 ± 0.04 mmol/L, P = 1.65 x 10-16, P = 5.89 x 1019 and P = 1.63 x 10-Is, respectively; Insulin： 1.47 ± 0.32 °tg/L, 2.66 ± 0.44 pg/L, 2.03 ± 0.29 pg/L and 4.17 ± 0.54 pg/L, P = 0.0001, P = 0.029 and P = 0.025, re- spectively）. However, these levels did not differ among the DM, T1 and T2 groups. The wet weight per unit length, wall thickness and opening angle of esophageal and intestinal segments in the DM group were signifi- cantly higher than those in the control group （from P = 0.009 to P = 0.004）. These parameters in the T1 group were significantly lower than those in the DM group （wet weight, duodenum： 0.147 ± 0.003 g/cm vs 0.158 ± 0.001 g/cm, P = 0.047; jejunum, 0.127 ± 0.003 g/cm vs 0.151：1：0.002 g/cm, P = 0.017; ileum, 0.127 ± 0.004 g/cm vs 0.139 ± 0.003 g/cm, P = 0.046; wall thickness, esophagus： 0.84±0.03 mm vs 0.94 ± 0.02 ram, P = 0.014; duodenum： 1.27 ± 0.06 mm vs 1.39 ± 0.05 ram, P = 0.031; jejunum： 1.19 ± 0.07 mm vs 1.34 ± 0.04 mm, P = 0.047; ileum： 1.09 ± 0.04 mm vs 1.15 ± 0.03 mm, P = 0.049; opening angle, esophagus： 112.2 ± 13.2° vs 134.7 ± 14.7°, P = 0.027; duodenum： 105.9 ± 12.3° vs 123.1 ± 13.1°, P = 0.046; jejunum： 90.1 ± 15.4° vs 115.5 ± 13.3°, P = 0.044; ileum： 112.9 ± 13.4° vs 136.1 ± 17.1°, P = 0.035）. In the esophageal and jejunal segments, the inner residual stain was significantly smaller and the outer residual strain was larger in the DN group than in the control group （P = 0.022 and P = 0.035）. T1 treatment significantly restored this biomechanical alteration （P = 0.011 and P = 0.019）, but T2 treatment did not. Fur- thermore, the circumferential and longitudinal stiffness of the esophageal and jejunal wall increased in the DM group compared with those in the control group. T1, but not T2 treatment, significantly decreased the cir- cumferential wall stiffness in the jejunal segment （P = 0.012） and longitudinal wall stiffness in the esophageal segment （P = 0.023）. The mRNA level of RAGE was significantly decreased in the T1 group compared to that in the DN group （P = 0.0069）. CONCLUSION： TWAJJ （high dose） treatment partly restored the morphometric and biomechanical remodel- ing of the upper gastrointestinal tract in diabetic rats.展开更多
AIM: To investigate which surgical techniques and perioperative regimens yielded the best survival rates for diabetic rats undergoing gastric bypass. METHODS: We performed Roux-en-Y gastric bypass with reserved gastri...AIM: To investigate which surgical techniques and perioperative regimens yielded the best survival rates for diabetic rats undergoing gastric bypass. METHODS: We performed Roux-en-Y gastric bypass with reserved gastric volume, a procedure in which gastrointestinal continuity was reestablished while excluding the entire duodenum and proximal jejunal loop. We observed the procedural success rate, long-term survival, and histopathological sequelae associated with a number of technical modifications. These included: use of anatomical markers to precisely identify Treitz's ligament; careful dissection along surgical planes; careful attention to the choice of regional transection sites; reconstruction using full-thickness anastomoses; use of a minimally invasive procedure with prohemostatic pretreatment and hemorrhage control; prevention of hypo-thermic damage; reduction in the length of the procedure; and accelerated surgical recovery using fast-track surgical modalities such as perioperative permissive underfeeding and goal-directed volume therapy. RESULTS: The series of modif ications we adopted reduced operation time from 110.02 ± 12.34 min to 78.39 ± 7.26 min (P < 0.01), and the procedural success rate increased from 43.3% (13/30) to 90% (18/20) (P < 0.01), with a long-term survival of 83.3% (15/18) (P < 0.01). CONCLUSION: Using a number of fast-track and damage control surgical techniques, we have successfully established a stable model of gastric bypass in diabetic rats.展开更多
Type 5 phosphodiesterase inhibitors （PDE51s） are well known being effective via the nitric oxide and cyclic guanosine monophosphate （NO-cGMP） pathway and are widely used in the treatment of diabetic erectile dysfu...Type 5 phosphodiesterase inhibitors （PDE51s） are well known being effective via the nitric oxide and cyclic guanosine monophosphate （NO-cGMP） pathway and are widely used in the treatment of diabetic erectile dysfunction （ED）. However, it is unclear whether other pathways may be involved in the treatment of diabetic ED with PDE51s. The purpose of this study was to clarify the role of antioxidants in diabetic ED treatment through the long-term administration of PDE51s. Three groups of Sprague-Dawley rats were utilized： Group N, the normal control; Group D, streptozotocin （STZ）-induced diabetic rats as a control; and Group D＋T, STZ-induced diabetic rats who received oral administration of tadalafil for 8 weeks. Erectile function was assessed by intracavernous pressure （ICP） and mean arterial pressure （MAP） during electrical stimulation of the cavernous nerve before euthanasia. The levels of malondialdehyde （MDA）, superoxide dismutase （SOD） and mitochondrial membrane potential （MMP） of cavernous tissue were assessed by biochemical analysis. The morphology of mitochondria was observed by electron microscopy. The ICP/MAP ratio was higher in Group D＋T than in Group D （P〈O.05）. The levels of MDA decreased and the activities of SOD increased in Group D＋T in comparison with Group D （P〈O.05）. The mitochondrial membrane potential level of cavernous tissue in diabetic rats was partially recovered by tadalafil treatment for 8 weeks. The morphology changes of mitochondria were also remarkably ameliorated in Group D＋T. Collectively, the long-term administration of tadalafil in diabetic rats partially reduced oxidative stress lesions of the penis via a local antioxidative stress pathway. Long-term dosages of tadalafil given once daily beginning soon after the onset of diabetes may aid in preventing rats from developing diabetic ED.展开更多
The small （SK3） and intermediate （IK 1） conductance calcium-activated potassium channels could have key roles in the endothelium-dependent hyperpolarization factor pathway, which is believed to contribute to norma...The small （SK3） and intermediate （IK 1） conductance calcium-activated potassium channels could have key roles in the endothelium-dependent hyperpolarization factor pathway, which is believed to contribute to normal penile erection function. We aimed to investigate the expression of SK3 and IK1 in diabetic rodents. The experimental diabetes model was induced in 8-week-old male Sprague-Dawley rats （250-300 g） by a single administration of streptozotocin. Both the diabetes mellitus group （DM group, n = 20） and the control group （NDM group, n = 10） were injected with a low dose of apomorphine to allow for the measurement and comparison of the corresponding penile erections. The mRNA and protein expression levels of SK3 and IK1 were measured by reverse transcription polymerase chain reaction and western blot, respectively. Erectile function was significantly decreased in the DM group compared with control group （P 〈 0.05）. The mRNA and protein expression levels of SK3 and IK1 were reduced in the cavernous tissue of diabetic rats compared with the control group （P 〈 0.05）. Diabetes inhibits mRNA and protein expression of both SK3 and IK1 in the cavernous tissue of diabetic rats. This could play a key role in the development of erectile dysfunction in diabetic rats.展开更多
A diabetes mellitus model was established through single intraperitoneal injection of streptozotocin into rats. Seven days later, model rats were intraperitoneally administered zinc protoporphyrin, a heme oxygenase-1 ...A diabetes mellitus model was established through single intraperitoneal injection of streptozotocin into rats. Seven days later, model rats were intraperitoneally administered zinc protoporphyrin, a heme oxygenase-1 inducer, and cobalt protoporphyrin, a heme oxygenase-1 inhibitor, once every two days, for 5 successive weeks. After administration, the paw withdrawal mechanical threshold of diabetic mellitus rats significantly decreased, the myelin sheath of the sciatic nerve thickened or showed vacuole defects, the number of spinal dorsal horn neurons reduced, some neurons degenerated and were necrotic, and heme oxygenase-1 was visible in the cytoplasm of spinal dorsal hom neurons. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling demonstrated that the number of apoptotic neurons increased, which could be inhibited by cobalt protoporphyrin, however, zinc protoporphyrin led to an opposite effect. Our experimental findings indicate that heme oxygenase-1 attenuates neuropathic pain in diabetic mellitus rats through amelioration of peripheral neuropathy and inhibition of spinal dorsal horn neuron apoptosis.展开更多
This study investigated the neuroprotective effect of Yiqi Bushen prescription （YQBS, supplementing qi and tonifying kidney） on neuronal cell apoptosis. Following YQBS treatment, the number of surviving hippocampal ...This study investigated the neuroprotective effect of Yiqi Bushen prescription （YQBS, supplementing qi and tonifying kidney） on neuronal cell apoptosis. Following YQBS treatment, the number of surviving hippocampal neurons increased, anti-apoptotic Bcl-2 expression increased and pro-apoptotic Bax expression decreased. In addition, diabetic rats exhibited improved learning and memory. YQBS treatment also increased Bcl-2 mRNA expression and the ratio of Bcl-2/Bax, but decreased levels of hypoxia-inducible factor-1α mRNA and Bax mRNA expression after high-glucose/hypoxia-induced injury. Results demonstrated that YQBS inhibited hippocampal neuronal apoptosis by decreasing hypoxia-inducible factor-1α expression and increasing Bcl-2 expression, thereby improving cognitive impairment in diabetic rats.展开更多
A rat model of diabetes mellitus was induced by a high fat diet, followed by focal brain ischemia induced using the thread method after 0.5 month. Immunohistochemistry showed that expression of receptor for advanced g...A rat model of diabetes mellitus was induced by a high fat diet, followed by focal brain ischemia induced using the thread method after 0.5 month. Immunohistochemistry showed that expression of receptor for advanced glycation end-products was higher in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Western blot assay revealed increased phosphorylated c-Jun N-terminal kinase expression, and unchanged phosphorylated extracellular signal-regulated protein kinase protein expression in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Additionally, phosphorylated p38 mitogen-activated protein kinase protein was not detected in any rats in the two groups. Severity of limb hemiplegia was worse in diabetic rats with brain ischemia compared with ischemia alone rats. The results suggest that increased expression of receptor for advanced glycation end-products can further activate the c-Jun N-terminal kinase pathway in mitogen-activated protein kinase, thereby worsening brain injury associated with focal brain ischemia in diabetic rats.展开更多
Diabetes mellitus significantly affects the male reproduction and sexual function. In the present study, we investigated the diabetes-induced dysfunction of seminal vesicles （SVs） in the diabetes-rat model and the r...Diabetes mellitus significantly affects the male reproduction and sexual function. In the present study, we investigated the diabetes-induced dysfunction of seminal vesicles （SVs） in the diabetes-rat model and the role of antioxidants. Streptozotocin-induced diabetes after 4 weeks caused smaller size of the organs, hypercontractility, histological abnormalities, increased concentrations of malondialdehyde in the serum and tissue, overexpression of oxidative stress markers, and cleaved caspase-3 as identified by immunohistochemistry in the SVs. In addition, diabetes resulted in deceased levels of serum testosterone and no newborns after the mating studies. Antioxidants significantly normalized all the above parameters, except for the severely decreased serum testosterone levels and the negative outcome of the mating studies. The present study gives evidence for the important role of diabetes-induced oxidative stress in the function and structure of these androgen-dependent organs. Antioxidants may be a promising supplementary therapy for diabetic male patients to alleviate ejaculatory disorders but alone is not efficient treatment for the mitigation of infertility.展开更多
Objective： We aimed to investigate protective effects ofvit E on oxidative stress status and homocysteine （Hey） in cardiac tissue of diabetic rats. Methods： Sixteen Wistar male rats were treated with STZ （strepto...Objective： We aimed to investigate protective effects ofvit E on oxidative stress status and homocysteine （Hey） in cardiac tissue of diabetic rats. Methods： Sixteen Wistar male rats were treated with STZ （streptozotocin） （60 mg/kg） to induce diabetes. Diabetic rats were divided into two groups： NTD （non-treated diabetic） and VETD （vit E-treated diabetic） rats. The VETD group received 300 mg/kg vit E with daily feeding. Eight normal rats of the same age were used as the control group. After 6 weeks, the rats were anesthetized, their cardiac tissue was removed, and homogenated supernatant was separated. Samples were assayed for TAC （total antioxidant capacity）, LPO （lipid peroxidation）, nitrite （NO2）, nitrate （NO3）, and Hcy. Key Findings： The contents of LPO, NO3 and Hcy in NTD compared to control group indicate a significant increase, but the levels of these parameters decreased in VETD （p 〈 0.05）. There was a significant decrease in the amount of TAC in the NTD group but in VETD group, that significantly increased （p 〈 0.05）. The amount of NO2 in NTD and VETD groups, compared to the control group, did not show any significant changes （p 〉 0.05）. Conclusions： Significant decrease of oxidative stress and Hey in the cardiac tissue caused by vit E supplementation strongly indicated that this radical scavenger may promote a protective effect on diabetic cardiomyopathy through the attenuation of oxidative stress and increase antioxidant defense mechanism.展开更多
Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor （CaSR） is expressed in testicular tissues and plays a pivotal role in calcium homeostasis b...Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor （CaSR） is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin （STZ, 40 mg kg-1） in Wistar rats. Animals then received GdCl3 （an agonist of CaSR, 8.67 mg kg-1）, NPS-2390 （an antagonist of CaSR, 0.20 g kg-~）, or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde （MDA）, lower superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH2-terminal protein kinase （JNK）, p38, and extracellular signaling-regulated kinase （ERK） 1/2. The above parameters could be further increased or aggravated by the administration of GdCI3, but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men.展开更多
The mRNA of insulin receptor （IR）, the insulin receptor substrates （IRSs）, glucose transporter 2 （GLUT2） and glucokinase （GK） in alloxan-induced diabetic rat livers were amplified by RT-PCR. The protein of the...The mRNA of insulin receptor （IR）, the insulin receptor substrates （IRSs）, glucose transporter 2 （GLUT2） and glucokinase （GK） in alloxan-induced diabetic rat livers were amplified by RT-PCR. The protein of the insulin receptor in rat livers was determined by westem-blotting. The results show that IR expression level decreased at the level of mRNA and protein. The gene expressions of IRSs, GLUT2 and GK changed significantly. The hepatic glycogen content in alloxan-diabetic rats treated with insulin （（13.2 ± 0.4） mg·g^-1） did not restore to normal level （（17.0 ±0.4） mg·g^-1） by means of anthrone-H2SO4 methods. The results imply that insulin resistance is developed during inchoate phase of alloxan-induced diabetic rats.展开更多
文摘Diabetes mellitus is a major public health concern. Finding a cure for the disease without its side-effects is the objective of modem medicine. The plant is a raw material for these studies. Zygophyllum gemini is a species widely used in Algeria to treat this disease. Our aim is to investigate the antidiabetic activity of aqueous extract and its fractions in induced diabetic Wistar rats by streptozotoein. The three drugs caused a decrease in blood sugar for 14 days. Butanolic fractions （BF） fraction gives significant results on blood glucose after seven days and significant regulating oral glucose tolerance. This preliminary study shows that Z. geslini is endowed with a remarkable antidiabetic activity and that further studies are needed.
文摘Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ on diabetic rats with ED and its potential mechanism viathe assessment of advanced glycosylation end products （AGEs）, autophagy, mTOR and the NO-cGMP pathway. Icarisid Ⅱ was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid Ⅱ group, rats were administered icarisid Ⅱ intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure （ICP/MAP）. AGE concentrations, nitric oxide synthase （NOS） activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 Iocalisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid Ⅱ increased ICP/MAP values, the smooth muscle cell （SMC） growth curve, S phase and SMC/collagen fibril （SMC/CF） proportions and decreased Beclin 1 （P〈0.05）. Icarisid Ⅱ significantly increased the proliferative index and p-p70S6K（Thr389） levels and decreased the numbers of autophagosomes and the levels of LC3-11 （P〈0.01）. Icarisid Ⅱ decreased AGE concentrations and increased cGMP concentration, NOS activity （P〈0.05） and cNOS levels （P〈0.01） in the diabetic ED group. Therefore, Icarisid Ⅱ constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.
文摘The present study investigated the effect of transplanting endothelial progenitor cells （EPCs） transfected with the vascular endothelial growth factor gene （VEGF165） into the corpora cavernosa of rats with diabetic erectile dysfunction （ED）. A rat model of diabetic ED was constructed via intraperitoneal injection of streptozotocin. After streptozotocin treatment, pre-treated EPCs from each of three groups of rats were transplanted into their corpora cavernosa. Our results, following intracavernosal pressure （ICP） monitoring, showed that ICP increased significantly among rats in the trial group when compared to the results from rats in the blank-plasmid and control groups during basal conditions and electrical stimulation （P〈O.01 for both comparisons）. Histological examination revealed extensive neovascularisation in the corpora cavernosa of rats in the trial group. Fluorescence microscopy indicated that many of the transplanted EPCs in the trial group survived, differentiated into endothelial cells and integrated into the sites of neovascularisation. Based on the results of this study, we conclude that transplantation of VEGF165-transfected EPCs into the corpora cavernosa of rats with diabetic ED restores erectile function.
基金This study was supported by the National Natural Science Foundation of China （No. 81170563）.
文摘The high incidence of erectile dysfunction （ED） in diabetes highlights a need for effective treatment strategies. Resveratrol, an activator of silent information regulator 2-related enzymes 1 （sirtuinl, SIRT1）, has received attention for its valuable effects in cancer, neurodegenerative diseases, longevity and cardiovascular disease. To explore the effects of resveratrol in diabetes-induced ED, resveratrol was administered to rats with streptozocin （65 mg kg-1）-induced diabetes. Erectile function, cavernous structure, tissue protein expression of silent information regulator 2-related enzymes 1 （sirtuinl, SIRT1）, p53 and forkhead transcription factor 0 3a （FOXO3a）, superoxide dismutase （SOD） activity and malondialdehyde （MDA） levels in the corpora cavernosa were studied. We found that SIRT1 was expressed in cavernosal tissue, and it was downregulated in the corpora of diabetic rats. The administration of resveratrol upregulated the expression of SI RT1 and restored erectile function. In contrast, resveratrol downregulated the expression of p53 and FOXO3a, which regulate apoptosis and oxidative stress. Furthermore, the resveratrol-treated group showed an improvement in smooth muscle content, SOD activity and MDA levels when compared with the diabetic group. Therefore, the ability of resveratrol to improve diabetes-induced ED is likely related to its activation of SIRT1 expression, thus causing the suppression of apoptosis and resistance towards oxidative stress.
基金Supported by National Natural Science Foundation of China,No. 81173259/H2708
文摘AIM： To investigate the effect of Tangweian Jianji （TWAJJ） on the biomechanical and morphometrical remodeling of the upper gastrointestinal tract in diabetic rats. METHODS： Diabetes was induced in 27 rats by in- jecting streptozotocin （40 mg/kg body weight）, the animals were then divided into three groups （n = 9 in each group）, i.e., diabetic control （DM）; high dose （10 g/kg, T1） and low dose （5 g/kg, T2）. Another 10 rats acted as normal controls （Control）. TWAJJ was admin- istered by gavage once daily. Blood glucose and serum insulin levels were measured. Circumferential length, wall thickness and opening angle were measured from esophageal, duodenal, jejunal and ileal ring segments. The residual strain was calculated from the morpho- metric data. Step-wise distension was carried out on esophageal and jejunal segments. The obtained data on the length, diameter and pressure changes were then used to calculate the circumferential and longitu- dinal stresses and strains. Real-time reverse transcrip- tion polymerase chain reaction was used to detect the receptor of advanced glycation end-products （RAGE） mRNA level in jejunal tissues. RESULTS： At the end of the experiment, the blood glucose level was significantly higher and the serum insulin level was significantly lower in DM, T1 and T2 groups than in the control group （Glucose： 30.23 ± 0.41 mmol/L, 27.48 ± 0.27 mmol/L and 27.84 ± 0.29 mmol/ L vs 5.05 ± 0.04 mmol/L, P = 1.65 x 10-16, P = 5.89 x 1019 and P = 1.63 x 10-Is, respectively; Insulin： 1.47 ± 0.32 °tg/L, 2.66 ± 0.44 pg/L, 2.03 ± 0.29 pg/L and 4.17 ± 0.54 pg/L, P = 0.0001, P = 0.029 and P = 0.025, re- spectively）. However, these levels did not differ among the DM, T1 and T2 groups. The wet weight per unit length, wall thickness and opening angle of esophageal and intestinal segments in the DM group were signifi- cantly higher than those in the control group （from P = 0.009 to P = 0.004）. These parameters in the T1 group were significantly lower than those in the DM group （wet weight, duodenum： 0.147 ± 0.003 g/cm vs 0.158 ± 0.001 g/cm, P = 0.047; jejunum, 0.127 ± 0.003 g/cm vs 0.151：1：0.002 g/cm, P = 0.017; ileum, 0.127 ± 0.004 g/cm vs 0.139 ± 0.003 g/cm, P = 0.046; wall thickness, esophagus： 0.84±0.03 mm vs 0.94 ± 0.02 ram, P = 0.014; duodenum： 1.27 ± 0.06 mm vs 1.39 ± 0.05 ram, P = 0.031; jejunum： 1.19 ± 0.07 mm vs 1.34 ± 0.04 mm, P = 0.047; ileum： 1.09 ± 0.04 mm vs 1.15 ± 0.03 mm, P = 0.049; opening angle, esophagus： 112.2 ± 13.2° vs 134.7 ± 14.7°, P = 0.027; duodenum： 105.9 ± 12.3° vs 123.1 ± 13.1°, P = 0.046; jejunum： 90.1 ± 15.4° vs 115.5 ± 13.3°, P = 0.044; ileum： 112.9 ± 13.4° vs 136.1 ± 17.1°, P = 0.035）. In the esophageal and jejunal segments, the inner residual stain was significantly smaller and the outer residual strain was larger in the DN group than in the control group （P = 0.022 and P = 0.035）. T1 treatment significantly restored this biomechanical alteration （P = 0.011 and P = 0.019）, but T2 treatment did not. Fur- thermore, the circumferential and longitudinal stiffness of the esophageal and jejunal wall increased in the DM group compared with those in the control group. T1, but not T2 treatment, significantly decreased the cir- cumferential wall stiffness in the jejunal segment （P = 0.012） and longitudinal wall stiffness in the esophageal segment （P = 0.023）. The mRNA level of RAGE was significantly decreased in the T1 group compared to that in the DN group （P = 0.0069）. CONCLUSION： TWAJJ （high dose） treatment partly restored the morphometric and biomechanical remodel- ing of the upper gastrointestinal tract in diabetic rats.
基金Supported by Scientific Research Fund of Heilongjiang Provincial Education Department, No. 11541200Harbin Medical University First Affi liated Hospital, No. 2007098
文摘AIM: To investigate which surgical techniques and perioperative regimens yielded the best survival rates for diabetic rats undergoing gastric bypass. METHODS: We performed Roux-en-Y gastric bypass with reserved gastric volume, a procedure in which gastrointestinal continuity was reestablished while excluding the entire duodenum and proximal jejunal loop. We observed the procedural success rate, long-term survival, and histopathological sequelae associated with a number of technical modifications. These included: use of anatomical markers to precisely identify Treitz's ligament; careful dissection along surgical planes; careful attention to the choice of regional transection sites; reconstruction using full-thickness anastomoses; use of a minimally invasive procedure with prohemostatic pretreatment and hemorrhage control; prevention of hypo-thermic damage; reduction in the length of the procedure; and accelerated surgical recovery using fast-track surgical modalities such as perioperative permissive underfeeding and goal-directed volume therapy. RESULTS: The series of modif ications we adopted reduced operation time from 110.02 ± 12.34 min to 78.39 ± 7.26 min (P < 0.01), and the procedural success rate increased from 43.3% (13/30) to 90% (18/20) (P < 0.01), with a long-term survival of 83.3% (15/18) (P < 0.01). CONCLUSION: Using a number of fast-track and damage control surgical techniques, we have successfully established a stable model of gastric bypass in diabetic rats.
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 30801143）, and by a grant from the overseas scholarship of Jiangsu Province, China （No. 2009K007）.
文摘Type 5 phosphodiesterase inhibitors （PDE51s） are well known being effective via the nitric oxide and cyclic guanosine monophosphate （NO-cGMP） pathway and are widely used in the treatment of diabetic erectile dysfunction （ED）. However, it is unclear whether other pathways may be involved in the treatment of diabetic ED with PDE51s. The purpose of this study was to clarify the role of antioxidants in diabetic ED treatment through the long-term administration of PDE51s. Three groups of Sprague-Dawley rats were utilized： Group N, the normal control; Group D, streptozotocin （STZ）-induced diabetic rats as a control; and Group D＋T, STZ-induced diabetic rats who received oral administration of tadalafil for 8 weeks. Erectile function was assessed by intracavernous pressure （ICP） and mean arterial pressure （MAP） during electrical stimulation of the cavernous nerve before euthanasia. The levels of malondialdehyde （MDA）, superoxide dismutase （SOD） and mitochondrial membrane potential （MMP） of cavernous tissue were assessed by biochemical analysis. The morphology of mitochondria was observed by electron microscopy. The ICP/MAP ratio was higher in Group D＋T than in Group D （P〈O.05）. The levels of MDA decreased and the activities of SOD increased in Group D＋T in comparison with Group D （P〈O.05）. The mitochondrial membrane potential level of cavernous tissue in diabetic rats was partially recovered by tadalafil treatment for 8 weeks. The morphology changes of mitochondria were also remarkably ameliorated in Group D＋T. Collectively, the long-term administration of tadalafil in diabetic rats partially reduced oxidative stress lesions of the penis via a local antioxidative stress pathway. Long-term dosages of tadalafil given once daily beginning soon after the onset of diabetes may aid in preventing rats from developing diabetic ED.
文摘The small （SK3） and intermediate （IK 1） conductance calcium-activated potassium channels could have key roles in the endothelium-dependent hyperpolarization factor pathway, which is believed to contribute to normal penile erection function. We aimed to investigate the expression of SK3 and IK1 in diabetic rodents. The experimental diabetes model was induced in 8-week-old male Sprague-Dawley rats （250-300 g） by a single administration of streptozotocin. Both the diabetes mellitus group （DM group, n = 20） and the control group （NDM group, n = 10） were injected with a low dose of apomorphine to allow for the measurement and comparison of the corresponding penile erections. The mRNA and protein expression levels of SK3 and IK1 were measured by reverse transcription polymerase chain reaction and western blot, respectively. Erectile function was significantly decreased in the DM group compared with control group （P 〈 0.05）. The mRNA and protein expression levels of SK3 and IK1 were reduced in the cavernous tissue of diabetic rats compared with the control group （P 〈 0.05）. Diabetes inhibits mRNA and protein expression of both SK3 and IK1 in the cavernous tissue of diabetic rats. This could play a key role in the development of erectile dysfunction in diabetic rats.
文摘A diabetes mellitus model was established through single intraperitoneal injection of streptozotocin into rats. Seven days later, model rats were intraperitoneally administered zinc protoporphyrin, a heme oxygenase-1 inducer, and cobalt protoporphyrin, a heme oxygenase-1 inhibitor, once every two days, for 5 successive weeks. After administration, the paw withdrawal mechanical threshold of diabetic mellitus rats significantly decreased, the myelin sheath of the sciatic nerve thickened or showed vacuole defects, the number of spinal dorsal horn neurons reduced, some neurons degenerated and were necrotic, and heme oxygenase-1 was visible in the cytoplasm of spinal dorsal hom neurons. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling demonstrated that the number of apoptotic neurons increased, which could be inhibited by cobalt protoporphyrin, however, zinc protoporphyrin led to an opposite effect. Our experimental findings indicate that heme oxygenase-1 attenuates neuropathic pain in diabetic mellitus rats through amelioration of peripheral neuropathy and inhibition of spinal dorsal horn neuron apoptosis.
基金the Science and Technology Development Program of Shandong Province, No.032050116the Natural Science Foundation of Shandong Province,No.ZR2010HM077the 20 Staff Foundation of 1020 Project of Shandong Province
文摘This study investigated the neuroprotective effect of Yiqi Bushen prescription （YQBS, supplementing qi and tonifying kidney） on neuronal cell apoptosis. Following YQBS treatment, the number of surviving hippocampal neurons increased, anti-apoptotic Bcl-2 expression increased and pro-apoptotic Bax expression decreased. In addition, diabetic rats exhibited improved learning and memory. YQBS treatment also increased Bcl-2 mRNA expression and the ratio of Bcl-2/Bax, but decreased levels of hypoxia-inducible factor-1α mRNA and Bax mRNA expression after high-glucose/hypoxia-induced injury. Results demonstrated that YQBS inhibited hippocampal neuronal apoptosis by decreasing hypoxia-inducible factor-1α expression and increasing Bcl-2 expression, thereby improving cognitive impairment in diabetic rats.
基金supported by the Science and Technology Development Foundation of Jilin Province,No.200905172
文摘A rat model of diabetes mellitus was induced by a high fat diet, followed by focal brain ischemia induced using the thread method after 0.5 month. Immunohistochemistry showed that expression of receptor for advanced glycation end-products was higher in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Western blot assay revealed increased phosphorylated c-Jun N-terminal kinase expression, and unchanged phosphorylated extracellular signal-regulated protein kinase protein expression in the ischemic cortex of diabetic rats compared with non-diabetic rats with brain ischemia. Additionally, phosphorylated p38 mitogen-activated protein kinase protein was not detected in any rats in the two groups. Severity of limb hemiplegia was worse in diabetic rats with brain ischemia compared with ischemia alone rats. The results suggest that increased expression of receptor for advanced glycation end-products can further activate the c-Jun N-terminal kinase pathway in mitogen-activated protein kinase, thereby worsening brain injury associated with focal brain ischemia in diabetic rats.
文摘Diabetes mellitus significantly affects the male reproduction and sexual function. In the present study, we investigated the diabetes-induced dysfunction of seminal vesicles （SVs） in the diabetes-rat model and the role of antioxidants. Streptozotocin-induced diabetes after 4 weeks caused smaller size of the organs, hypercontractility, histological abnormalities, increased concentrations of malondialdehyde in the serum and tissue, overexpression of oxidative stress markers, and cleaved caspase-3 as identified by immunohistochemistry in the SVs. In addition, diabetes resulted in deceased levels of serum testosterone and no newborns after the mating studies. Antioxidants significantly normalized all the above parameters, except for the severely decreased serum testosterone levels and the negative outcome of the mating studies. The present study gives evidence for the important role of diabetes-induced oxidative stress in the function and structure of these androgen-dependent organs. Antioxidants may be a promising supplementary therapy for diabetic male patients to alleviate ejaculatory disorders but alone is not efficient treatment for the mitigation of infertility.
文摘Objective： We aimed to investigate protective effects ofvit E on oxidative stress status and homocysteine （Hey） in cardiac tissue of diabetic rats. Methods： Sixteen Wistar male rats were treated with STZ （streptozotocin） （60 mg/kg） to induce diabetes. Diabetic rats were divided into two groups： NTD （non-treated diabetic） and VETD （vit E-treated diabetic） rats. The VETD group received 300 mg/kg vit E with daily feeding. Eight normal rats of the same age were used as the control group. After 6 weeks, the rats were anesthetized, their cardiac tissue was removed, and homogenated supernatant was separated. Samples were assayed for TAC （total antioxidant capacity）, LPO （lipid peroxidation）, nitrite （NO2）, nitrate （NO3）, and Hcy. Key Findings： The contents of LPO, NO3 and Hcy in NTD compared to control group indicate a significant increase, but the levels of these parameters decreased in VETD （p 〈 0.05）. There was a significant decrease in the amount of TAC in the NTD group but in VETD group, that significantly increased （p 〈 0.05）. The amount of NO2 in NTD and VETD groups, compared to the control group, did not show any significant changes （p 〉 0.05）. Conclusions： Significant decrease of oxidative stress and Hey in the cardiac tissue caused by vit E supplementation strongly indicated that this radical scavenger may promote a protective effect on diabetic cardiomyopathy through the attenuation of oxidative stress and increase antioxidant defense mechanism.
文摘Male infertility caused by testicular damage is one of the complications of diabetes mellitus. The calcium-sensing receptor （CaSR） is expressed in testicular tissues and plays a pivotal role in calcium homeostasis by activating cellular signaling pathways, but its role in testicular damage induced by diabetes remains unclear. A diabetic model was established by a single intraperitoneal injection of streptozotocin （STZ, 40 mg kg-1） in Wistar rats. Animals then received GdCl3 （an agonist of CaSR, 8.67 mg kg-1）, NPS-2390 （an antagonist of CaSR, 0.20 g kg-~）, or a combination of both 2 months after STZ injection. Diabetic rats had significantly lower testes weights and serum levels of testosterone compared to healthy rats, indicating testicular damage and dysfunction in STZ-induced diabetic rats. Compared with healthy controls, the testicular tissues of diabetic rats overexpressed the CaSR protein and had higher levels of malondialdehyde （MDA）, lower superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） activity, and higher numbers of apoptotic germ cells. The testicular tissues from diabetic rats also expressed lower levels of Bcl-2 and higher levels of Bax and cleaved caspase-3 in addition to higher phosphorylation rates of c-Jun NH2-terminal protein kinase （JNK）, p38, and extracellular signaling-regulated kinase （ERK） 1/2. The above parameters could be further increased or aggravated by the administration of GdCI3, but could be attenuated by injection of NPS-2390. In conclusion, the present results indicate that CaSR activation participates in diabetes-induced testicular damage, implying CaSR may be a potential target for protective strategies against diabetes-induced testicular damage and could help to prevent infertility in diabetic men.
基金Supported by the National Natural Science Foundation of China (20671037, 20371018)
文摘The mRNA of insulin receptor （IR）, the insulin receptor substrates （IRSs）, glucose transporter 2 （GLUT2） and glucokinase （GK） in alloxan-induced diabetic rat livers were amplified by RT-PCR. The protein of the insulin receptor in rat livers was determined by westem-blotting. The results show that IR expression level decreased at the level of mRNA and protein. The gene expressions of IRSs, GLUT2 and GK changed significantly. The hepatic glycogen content in alloxan-diabetic rats treated with insulin （（13.2 ± 0.4） mg·g^-1） did not restore to normal level （（17.0 ±0.4） mg·g^-1） by means of anthrone-H2SO4 methods. The results imply that insulin resistance is developed during inchoate phase of alloxan-induced diabetic rats.
