目的:探讨了糖基化终末产物(advanced glycation end products,AGE)及其受体(receptor for advanced glycation end products,RAGE)在糖尿病大鼠胃组织中的分布.方法:糖尿病模型组与正常组大鼠饲养8w k,测量空腹血糖、糖化血清蛋白、胃...目的:探讨了糖基化终末产物(advanced glycation end products,AGE)及其受体(receptor for advanced glycation end products,RAGE)在糖尿病大鼠胃组织中的分布.方法:糖尿病模型组与正常组大鼠饲养8w k,测量空腹血糖、糖化血清蛋白、胃壁组织学,免疫组织化学检测AGE与RAGE在胃壁组织的表达.结果:模型组大鼠胃黏膜层(781.47μm±137.82μm vs 709.85μm±169.41μm)和黏膜下层(233.39μm±134.05μm vs109.32μm±44.43μm)的厚度较正常组显著增加(P<0.05);AGE与RAGE在模型组大鼠胃组织的黏膜层(5.66±1.90 vs 2.25±0.52,2.79±0.54 vs 1.70±0.30)和肌层(37.37±7.38 vs 24.32±4.02,4.26±0.80vs 3.59±0.37)的分布较正常组显著增加(P<0.05).结论:AGE与RAGE在糖尿病大鼠的胃组织中表达上调,该异常分布可能与糖尿病胃肠功能障碍有关.展开更多
目的:研究糖基化终末产物(advanced glycation end products,AGE)及其受体(receptor for advanced glycation end products,RAGE)在胃肠道中的分布,为进一步探索其在慢性糖尿病胃肠功能紊乱中的作用奠定基础.方法:分别对成年Wistar大鼠...目的:研究糖基化终末产物(advanced glycation end products,AGE)及其受体(receptor for advanced glycation end products,RAGE)在胃肠道中的分布,为进一步探索其在慢性糖尿病胃肠功能紊乱中的作用奠定基础.方法:分别对成年Wistar大鼠食管、胃、十二指肠、空肠、回肠、结肠及直肠组织进行AGE及RAGE免疫组织化学染色.结果:(1)食管:AGE及RAGE主要分布在横纹肌的肌细胞及黏膜的鳞状上皮细胞;(2)胃:AGE在壁细胞为强阳性.RAGE在主细胞、肥大细胞、神经细胞为强阳性,在壁细胞为中等强度阳性,在表面黏液细胞为弱阳性;(3)小肠:AGE及RAGE在绒毛及固有层上皮细胞为阳性或强阳性.RAGE在肠道的神经细胞亦为强阳性;(4)结肠及直肠:AGE及RAGE在黏膜上皮细胞为弱阳性,RAGE在神经细胞为强阳性.结论:AGE及RAGE广泛分布于肠道上皮细胞及食管的横纹肌细胞,AGE亦分布于胃的壁细胞,RAGE亦分布于胃的壁细胞、主细胞、表面黏液细胞、肥大细胞及胃肠道的神经细胞.展开更多
Gastric accommodation is important for the understanding of the pathophysiology in functional dyspepsia and is also relevant for symptom generation in other disorders. The term gastric accommodation has at least three...Gastric accommodation is important for the understanding of the pathophysiology in functional dyspepsia and is also relevant for symptom generation in other disorders. The term gastric accommodation has at least three different meanings： The accommodation process, the accommodation reflex, and the accommodation response. The gastric accommodation process is a complex phenomenon that describes how the size of the gastric compartment changes in response to a meal. The electronic barostat is considered the gold standard in assessing gastric accommodation. Imaging methods, including MRI, SPECT, and ultrasonography may also be used, particularly in patients who are stress-responsive, e.g. functional dyspepsia patients, as a non-invasive and less stress-inducing method is favourable. Ultrasonography satisfies these criteria as it does not by itself distort the physiological response in stress-responsive individuals.展开更多
AIM: To investigate that both the neuronal function of the contractile system and structural apparatus of the gastrointestinal tract are affected in patients with longstanding diabetes and auto mic neuropathy. METHODS...AIM: To investigate that both the neuronal function of the contractile system and structural apparatus of the gastrointestinal tract are affected in patients with longstanding diabetes and auto mic neuropathy. METHODS: The evoked esophageal and duodenal contractile activity to standardized bag distension was assessed using a specialized ultrasound-based probe. Twelve type-1 diabetic patients with autonomic neuropathy and severe gastrointestinal symptoms and 12 healthy controls were studied. The geometry and biomechanical parameters (strain, tension/stress, and stiffness) were assessed. RESULTS: The diabetic patients had increased frequency of distension-induced contractions (6.0 ± 0.6 vs 3.3 ± 0.5, P < 0.001). This increased reactivity was correlated with the duration of the disease (P = 0.009). Impaired coordination of the contractile activity in diabetic patients was demonstrated as imbalance between the time required to evoke the first contraction at the distension site and proximal to it (1.5 ± 0.6 vs 0.5 ± 0.1, P = 0.03). The esophageal wall and especially the mucosa-submucosa layer had increased thickness in the patients (P < 0.001), and the longitudinal and radial compressive stretch was less in diabetics (P <0.001). The esophageal and duodenal wall stiffness and circumferential deformation induced by the distensions were not affected in the patients (all P > 0.14). CONCLUSION: The impaired contractile activity with an imbalance in the distension-induced contractions likely reflects neuronal abnormalities due to autonomic neuropathy. However, structural changes and remodeling of the gastrointestinal tract are also evident and may add to the neuronal changes. This may contribute to the pathophysiology of diabetic gut dysfunction and impact on future management of diabetic patients with gastrointestinal symptoms.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 the effect of a Chinese medicine, Kaiyu Qingwei Jianji （KYQWJJ） used for diabetic treatment, on the morphometry and residual strain distribution of the small intestine in streptozotocin （STZ） ...AIM： To investigate the effect of a Chinese medicine, Kaiyu Qingwei Jianji （KYQWJJ） used for diabetic treatment, on the morphometry and residual strain distribution of the small intestine in streptozotocin （STZ） -induced diabetic rats. Correlation analysis was also performed between the opening angle and residual strain with the blood glucose level. METHODS： Forty-two male Wistar rats weighing 220-240 g were included in this study. Thirty-two STZ- induced diabetic rats were subdivided into four groups （n = 8 in each group）, i.e. diabetic control group （DM）; high dose of KYQWJJ （T1, 36g/kg per day）; low dose of KYQWJJ （T2, 17 g/kg per day） and Gliclazide （T3, 50 mg/kg per day）. Another ten rats were used as nondiabetic control （CON）. The medicines were poured directly into stomach lumen by gastric lavage twice daily. The rats of CON and DM groups were only poured the physiological saline. Blood glucose and plasma insulin levels were measured. Experimental period was 35 d. At the end of experiment, three 5-cm long segments were harvested from the duodenum, jejunum and ileum. Three rings of 1-2 mm in length for no-load and zero-stress state tests were cut from the middle of different segments. The morphometric data, such as the circumferential length, the wall thickness and the opening angle were measured from the digitized images of intestinal segments in the no-load state and zerostress state. The residual strain was computed from the morphometry data. Furthermore, the linear regression analysis was performed between blood glucose level with morphometric and biomechanical data in the different intestinal segments. RESULTS： The blood glucose level of DM group was consistent 4-fold to 5-fold higher than those in CON group during the experiment （16.89 ± 1.11 vs 3.44 ± 0.15 mmol/L, P 〈 0.001）. The blood glucose level in the T1 （16.89 ± 1.11 vs 11.08 ± 2.67 mmol/L, P 〈 0.01） and T3 groups （16.89 ± 1.11 vs 13.54 ± 1.73 mmol/L, P 〈 0.05）, but not in T2 group （P 〉 0.05） was significantly lower than those in DM group. The plasma insulin levels of DM, T1, T2 and T3 groups were significantly lower than those in CON group （10.98 ± 1.02, 12.52 ± 1.42,13.54 ± 1.56,10.96 ± 0.96 vs 17.84 ± 2.34 pmol/L respectively, P 〈 0.05）, but no significantly difference among the groups with exception of CON group. The wet weight/cm and total wall thickness of duodenum, jejunum and ileum in DM group were significantly higher than those in CON group （wet weight （g/cm）： duodenum 0.209 ± 0.012 vs 0.166 ± 0.010, jejunum 0.149 ± 0.008 vs 0.121 ± 0.004, ileum 0.134 ± 0.013 vs 0.112 ± 0.007; Wall thickness （mm）： duodenum 0.849 ± 0.027 vs 0.710 ± 0.026, jejunum 0.7259 ± 0.034 vs 0.627 ± 0.025, ileum 0.532 ± 0.023 vs 0.470 ± 0.010, all P 〈 0.05）, T1 and T3 treatment could partly restore change of wall thickness, but T2 could not. The opening angle and absolute value of inner and outer residual stain were significantly smaller in duodenal segment （188 ± 11 degrees, -0.31 ± 0.02 and 0.35 ± 0.03 vs 259 ± 15 degrees, -0.40 ± 0.02 and 0.43 ± 0.05） and larger in jejunal （215 ± 20 degrees, -0.30 ± 0.03 and 0.36 ± 0.06 vs 172 ± 19 degrees, -0.25 ± 0.02 and 0.27 ± 0.02） and ileal segments （183 ± 20 degrees, -0.28 ± 0.01 and 0.34 ± 0.05 vs 153 ± 14 degrees, -0.23 ± 0.03 and 0.29 ± 0.04） in DM group than in CON group （P 〈 0.01）. TI and T3 treatment could partly restore this biomechanical alteration, but strong effect was found in T1 treatment （duodenum 243 ± 14 degrees, -0.36 ± 0.02 and 0.42 ± 0.06, jejunum 180 ± 15 degrees, -0.26 ± 0.03 and 0.30 ± 0.06 and ileum 163 ± 17 degrees, -0.23 ± 0.03 and 0.30 ± 0.05, compared with DM, P 〈 0.05）. The linear association was found between the glucose level with most morphometric and biomechanical data. CONCLUSION： KYQWJJ （high dose） treatment could partly restore the changes of blood glucose level and the remodeling of morphometry and residual strain of small intestine in diabetic rats. The linear regression analysis demonstrated that the effect of KYQWJJ on intestinal opening angle and residual strain is partially through its effect on the blood glucose level.展开更多
Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechan...Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechanical, electrical, thermal and chemical methods in visceral pain research are discussed with emphasis of combinations (e.g., the multimodal approach). The methods have been used widely in assessment of pain mechanisms in the esophagus and have contributed to our understanding of the symptoms reported in these patients. Hence abnormal activation and plastic changes of central pain pathways seem to play a major role in the symptoms in some patients with gastro-esophageal reflux disease and in patients with functional chest pain of esophageal origin. These findings may lead to an alternative approach for treatment in patients that does not respond to conventional medical or surgical therapy.展开更多
AIM:To investigate changes in advanced glycation end products(AGEs) and their receptor(RAGE) expression in the gastrointestinal(GI) tract in type 2 diabetic rats.METHODS:Eight inherited type 2 diabetic rats GotoKakiza...AIM:To investigate changes in advanced glycation end products(AGEs) and their receptor(RAGE) expression in the gastrointestinal(GI) tract in type 2 diabetic rats.METHODS:Eight inherited type 2 diabetic rats GotoKakizak(GK) and ten age-matched normal rats were used in the study.From 18 wk of age,the body weight and blood glucose were measured every week and 2 wk respectively.When the rats reached 32 wk,twocentimeter segments of esophagus,duodenum,jejunum,ileum,and colon were excised and the wet weight was measured.The segments were fixed in 10% formalin,embedded in paraffin and five micron sections were cut.The layer thickness was measured in Hematoxylin and Eosin-stained slides.AGE [N epsilon-(carboxymethyl) lysine and N epsilon-(carboxyethyl)lysine] and RAGE were detected by immunohistochemistry staining and image analysis was done using Sigmascan Pro 4.0 image analysis software.RESULTS:The blood glucose concentration(mmol/L) at 18 wk age was highest in the GK group(8.88 ± 1.87 vs 6.90 ± 0.43,P < 0.001),a difference that continued to exist until the end of the experiment.The wet weight per unit length(mg/cm) increased in esophagus,jejunum and colon from the normal to the GK group(60.64 ± 9.96 vs 68.56 ± 11.69,P < 0.05 for esophagus; 87.01 ± 9.35 vs 105.29 ± 15.45,P < 0.01 for jejunum; 91.37 ± 7.25 vs 97.28 ± 10.90,P < 0.05 for colon).Histologically,the layer thickness of the GItract was higher for esophagus,jejunum and colon in the GK group [full thickness(μm):575.37 ± 69.22 vs 753.20 ± 150.41,P < 0.01 for esophagus; 813.51 ± 44.44 vs 884.81 ± 45.31,P < 0.05 for jejunum; 467.12 ± 65.92 vs 572.26 ± 93.60,P < 0.05 for colon].In esophagus,the AGE and RAGE mainly distributed in striated muscle cells and squamous epithelial cells.The AGE distribution was much stronger in the GK group compared to the normal group both in the striated muscle layer and mucosa layer(immuno-positive area/ total measuring area %:4.52 ± 0.89 vs 10.96 ± 1.34,P < 0.01 for muscle; 8.90 ± 2.62 vs 22.45 ± 1.26,P < 0.01 for mucosa).No visible difference was found for RAGE distribution between the two groups.In the intestine AGE and RAGE distributed in epithelial cells of villi and crypt.RAGE was also found in neurons in the myenteric and submucosal plexus.The intensity of AGE staining in mucosa of all segments and RAGE staining in neurons in all segments were strongest in the diabetes group.Significant difference for AGE was found in the epithelial cells of villi and crypt in duodenum(immunopositive area/total measuring area %:13.37 ± 3.51 vs 37.48 ± 8.43,P < 0.05 for villi; 0.38 ± 0.12 vs 1.87 ± 0.53,P < 0.05 for crypt) and for RAGE in neurons of all segments(e.g.,for jejunum:no staining neurons% 0 vs 0,mild 36.0 ± 5.2 vs 28.7 ± 3.5,moderate 53.2 ± 4.8 vs 55.8 ± 5.4,strong 10.7 ± 1.1 vs 15.4 ± 2.0,P < 0.05).In the colon,RAGE was primarily found in neurons in the myenteric and submucosal plexus.It was stronger in the diabetes group than in the normal group(no staining neurons% 6.2 ± 0.2 vs 0.3 ± 0.04,mild 14.9 ± 2.1 vs 17.6 ± 1.5,moderate 53.1 ± 4.6 vs 44.7 ± 4.4,strong 25.6 ± 18 vs 43.6 ± 4.0,P < 0.05).In the rectum,RAGE was primarily found in the mucosa epithelial cells.CONCLUSION:The AGE and RAGE expression was upregulated in the GI tract of GK diabetic rats and may contribute to GI dysfunction in type 2 diabetic patients.展开更多
Understanding and characterization of pain and other sensory symptoms are among the most important issues in the diagnosis and assessment of patient with gastrointestinal disorders. Methods to evoke and assess experim...Understanding and characterization of pain and other sensory symptoms are among the most important issues in the diagnosis and assessment of patient with gastrointestinal disorders. Methods to evoke and assess experimental pain have recently developed into a new area with the possibility for multimodal stimulation （e.g., electrical, mechanical, thermal and chemical stimulation） of different nerves and pain pathways in the human gut. Such methods mimic to a high degree the pain experienced in the clinic. Multimodal pain methods have increased our basic understanding of different peripheral receptors in the gut in health and disease. Together with advanced muscle analysis, the methods have increased our understanding of receptors sensitive to mechanical, chemical and temperature stimuli in diseases, such as systemic sclerosis and diabetes. The methods can also be used to unravel central pain mechanisms, such as those involved in allodynia, hyperalgesia and referred pain. Abnormalities in central pain mechanisms are often seen in patients with chronic gut pain and hence methods relying on multimodal pain stimulation may help to understand the symptoms in these patients. Sex differences have been observed in several diseases of the gut, and differences in central pain processing between males and females have been hypothesized using multimodal pain stimulations. Finally, multimodal methods have recently been used to gain more insight into the effect of drugs against pain in the GI tract. Hence, the multimodal methods undoubtedly represents a major step forward in the future characterization and treatment of patients with various diseases of the gut.展开更多
Barrett's esophagus (BE) is characterized by intestinal metaplasia with the differentiated epithelium replaced by another type of epithelium morphologically similar to normal intestinal epithelium. The metaplasia ...Barrett's esophagus (BE) is characterized by intestinal metaplasia with the differentiated epithelium replaced by another type of epithelium morphologically similar to normal intestinal epithelium. The metaplasia is preceded by bile and acid reflux into the esophagus. BE is a premalignant condition associated with increased risk of esophageal cancer, especially esophageal adenocarcinoma. The Caudal-related homeodomain transcription factors Caudal-related homeodomain transcription factor CDX1 and CDX2 are expressed exclusively in the small and large intestine, playing important roles in proliferation and differentiation of intestinal epithelial cells. Ectopic expression of CDX1 and CDX2 occurs in BE. The apical sodium-dependent bile acid transporter (ASBT) is expressed primarily in terminal ileum where it is a key factor for intestinal reabsorption of bile salts. In addition to upregulation of CDX1 and CDX2, ASBT expression is up-regulated in BE. Furthermore, both CDX1/CDX2 and ASBT expressions are down-regulated in high-grade esophageal dysplasia. The alteration of the above-mentioned factors calls for attention: what is the relationship between CDXs and ASBT aberrant expression in BE? In this commentary, we discuss this issue on basis of the recent study done by Ma et al .展开更多
The gastrointestinal (GI) tract is the system of organs within multi-cellular animals that takes in food, digests it to extract energy and nutrients, and expels the remaining waste. The various patterns of GI tract fu...The gastrointestinal (GI) tract is the system of organs within multi-cellular animals that takes in food, digests it to extract energy and nutrients, and expels the remaining waste. The various patterns of GI tract function are generated by the integrated behaviour of multiple tissues and cell types. A thorough study of the GI tract requires understanding of the interactions between cells, tissues and gastrointestinal organs in health and disease. This depends on knowledge, not only of numerous cellular ionic current mechanisms and signal transduction pathways, but also of large scale GI tissue structures and the special distribution of the nervous network. A unique way of coping with this explosion in complexity is mathematical and computational modelling; providing a computational framework for the multilevel modelling and simulation of the human gastrointestinal anatomy and physiology. The aim of this review is to describe the current status of biomechanical modelling work of the GI tract in humans and animals, which can be further used to integrate the physiological, anatomical and medical knowledge of the GI system. Such modelling will aid research and ensure that medical professionals benefit, through the provision of relevant and precise information about the patient's condition and GI remodelling in animal disease models. It will also improve the accuracy and efficiency of medical procedures, which could result in reduced cost for diagnosis and treatment.展开更多
文摘目的:探讨了糖基化终末产物(advanced glycation end products,AGE)及其受体(receptor for advanced glycation end products,RAGE)在糖尿病大鼠胃组织中的分布.方法:糖尿病模型组与正常组大鼠饲养8w k,测量空腹血糖、糖化血清蛋白、胃壁组织学,免疫组织化学检测AGE与RAGE在胃壁组织的表达.结果:模型组大鼠胃黏膜层(781.47μm±137.82μm vs 709.85μm±169.41μm)和黏膜下层(233.39μm±134.05μm vs109.32μm±44.43μm)的厚度较正常组显著增加(P<0.05);AGE与RAGE在模型组大鼠胃组织的黏膜层(5.66±1.90 vs 2.25±0.52,2.79±0.54 vs 1.70±0.30)和肌层(37.37±7.38 vs 24.32±4.02,4.26±0.80vs 3.59±0.37)的分布较正常组显著增加(P<0.05).结论:AGE与RAGE在糖尿病大鼠的胃组织中表达上调,该异常分布可能与糖尿病胃肠功能障碍有关.
文摘目的:研究糖基化终末产物(advanced glycation end products,AGE)及其受体(receptor for advanced glycation end products,RAGE)在胃肠道中的分布,为进一步探索其在慢性糖尿病胃肠功能紊乱中的作用奠定基础.方法:分别对成年Wistar大鼠食管、胃、十二指肠、空肠、回肠、结肠及直肠组织进行AGE及RAGE免疫组织化学染色.结果:(1)食管:AGE及RAGE主要分布在横纹肌的肌细胞及黏膜的鳞状上皮细胞;(2)胃:AGE在壁细胞为强阳性.RAGE在主细胞、肥大细胞、神经细胞为强阳性,在壁细胞为中等强度阳性,在表面黏液细胞为弱阳性;(3)小肠:AGE及RAGE在绒毛及固有层上皮细胞为阳性或强阳性.RAGE在肠道的神经细胞亦为强阳性;(4)结肠及直肠:AGE及RAGE在黏膜上皮细胞为弱阳性,RAGE在神经细胞为强阳性.结论:AGE及RAGE广泛分布于肠道上皮细胞及食管的横纹肌细胞,AGE亦分布于胃的壁细胞,RAGE亦分布于胃的壁细胞、主细胞、表面黏液细胞、肥大细胞及胃肠道的神经细胞.
文摘Gastric accommodation is important for the understanding of the pathophysiology in functional dyspepsia and is also relevant for symptom generation in other disorders. The term gastric accommodation has at least three different meanings： The accommodation process, the accommodation reflex, and the accommodation response. The gastric accommodation process is a complex phenomenon that describes how the size of the gastric compartment changes in response to a meal. The electronic barostat is considered the gold standard in assessing gastric accommodation. Imaging methods, including MRI, SPECT, and ultrasonography may also be used, particularly in patients who are stress-responsive, e.g. functional dyspepsia patients, as a non-invasive and less stress-inducing method is favourable. Ultrasonography satisfies these criteria as it does not by itself distort the physiological response in stress-responsive individuals.
文摘AIM: To investigate that both the neuronal function of the contractile system and structural apparatus of the gastrointestinal tract are affected in patients with longstanding diabetes and auto mic neuropathy. METHODS: The evoked esophageal and duodenal contractile activity to standardized bag distension was assessed using a specialized ultrasound-based probe. Twelve type-1 diabetic patients with autonomic neuropathy and severe gastrointestinal symptoms and 12 healthy controls were studied. The geometry and biomechanical parameters (strain, tension/stress, and stiffness) were assessed. RESULTS: The diabetic patients had increased frequency of distension-induced contractions (6.0 ± 0.6 vs 3.3 ± 0.5, P < 0.001). This increased reactivity was correlated with the duration of the disease (P = 0.009). Impaired coordination of the contractile activity in diabetic patients was demonstrated as imbalance between the time required to evoke the first contraction at the distension site and proximal to it (1.5 ± 0.6 vs 0.5 ± 0.1, P = 0.03). The esophageal wall and especially the mucosa-submucosa layer had increased thickness in the patients (P < 0.001), and the longitudinal and radial compressive stretch was less in diabetics (P <0.001). The esophageal and duodenal wall stiffness and circumferential deformation induced by the distensions were not affected in the patients (all P > 0.14). CONCLUSION: The impaired contractile activity with an imbalance in the distension-induced contractions likely reflects neuronal abnormalities due to autonomic neuropathy. However, structural changes and remodeling of the gastrointestinal tract are also evident and may add to the neuronal changes. This may contribute to the pathophysiology of diabetic gut dysfunction and impact on future management of diabetic patients with gastrointestinal symptoms.
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.
文摘AIM： To investigate the effect of a Chinese medicine, Kaiyu Qingwei Jianji （KYQWJJ） used for diabetic treatment, on the morphometry and residual strain distribution of the small intestine in streptozotocin （STZ） -induced diabetic rats. Correlation analysis was also performed between the opening angle and residual strain with the blood glucose level. METHODS： Forty-two male Wistar rats weighing 220-240 g were included in this study. Thirty-two STZ- induced diabetic rats were subdivided into four groups （n = 8 in each group）, i.e. diabetic control group （DM）; high dose of KYQWJJ （T1, 36g/kg per day）; low dose of KYQWJJ （T2, 17 g/kg per day） and Gliclazide （T3, 50 mg/kg per day）. Another ten rats were used as nondiabetic control （CON）. The medicines were poured directly into stomach lumen by gastric lavage twice daily. The rats of CON and DM groups were only poured the physiological saline. Blood glucose and plasma insulin levels were measured. Experimental period was 35 d. At the end of experiment, three 5-cm long segments were harvested from the duodenum, jejunum and ileum. Three rings of 1-2 mm in length for no-load and zero-stress state tests were cut from the middle of different segments. The morphometric data, such as the circumferential length, the wall thickness and the opening angle were measured from the digitized images of intestinal segments in the no-load state and zerostress state. The residual strain was computed from the morphometry data. Furthermore, the linear regression analysis was performed between blood glucose level with morphometric and biomechanical data in the different intestinal segments. RESULTS： The blood glucose level of DM group was consistent 4-fold to 5-fold higher than those in CON group during the experiment （16.89 ± 1.11 vs 3.44 ± 0.15 mmol/L, P 〈 0.001）. The blood glucose level in the T1 （16.89 ± 1.11 vs 11.08 ± 2.67 mmol/L, P 〈 0.01） and T3 groups （16.89 ± 1.11 vs 13.54 ± 1.73 mmol/L, P 〈 0.05）, but not in T2 group （P 〉 0.05） was significantly lower than those in DM group. The plasma insulin levels of DM, T1, T2 and T3 groups were significantly lower than those in CON group （10.98 ± 1.02, 12.52 ± 1.42,13.54 ± 1.56,10.96 ± 0.96 vs 17.84 ± 2.34 pmol/L respectively, P 〈 0.05）, but no significantly difference among the groups with exception of CON group. The wet weight/cm and total wall thickness of duodenum, jejunum and ileum in DM group were significantly higher than those in CON group （wet weight （g/cm）： duodenum 0.209 ± 0.012 vs 0.166 ± 0.010, jejunum 0.149 ± 0.008 vs 0.121 ± 0.004, ileum 0.134 ± 0.013 vs 0.112 ± 0.007; Wall thickness （mm）： duodenum 0.849 ± 0.027 vs 0.710 ± 0.026, jejunum 0.7259 ± 0.034 vs 0.627 ± 0.025, ileum 0.532 ± 0.023 vs 0.470 ± 0.010, all P 〈 0.05）, T1 and T3 treatment could partly restore change of wall thickness, but T2 could not. The opening angle and absolute value of inner and outer residual stain were significantly smaller in duodenal segment （188 ± 11 degrees, -0.31 ± 0.02 and 0.35 ± 0.03 vs 259 ± 15 degrees, -0.40 ± 0.02 and 0.43 ± 0.05） and larger in jejunal （215 ± 20 degrees, -0.30 ± 0.03 and 0.36 ± 0.06 vs 172 ± 19 degrees, -0.25 ± 0.02 and 0.27 ± 0.02） and ileal segments （183 ± 20 degrees, -0.28 ± 0.01 and 0.34 ± 0.05 vs 153 ± 14 degrees, -0.23 ± 0.03 and 0.29 ± 0.04） in DM group than in CON group （P 〈 0.01）. TI and T3 treatment could partly restore this biomechanical alteration, but strong effect was found in T1 treatment （duodenum 243 ± 14 degrees, -0.36 ± 0.02 and 0.42 ± 0.06, jejunum 180 ± 15 degrees, -0.26 ± 0.03 and 0.30 ± 0.06 and ileum 163 ± 17 degrees, -0.23 ± 0.03 and 0.30 ± 0.05, compared with DM, P 〈 0.05）. The linear association was found between the glucose level with most morphometric and biomechanical data. CONCLUSION： KYQWJJ （high dose） treatment could partly restore the changes of blood glucose level and the remodeling of morphometry and residual strain of small intestine in diabetic rats. The linear regression analysis demonstrated that the effect of KYQWJJ on intestinal opening angle and residual strain is partially through its effect on the blood glucose level.
基金Supported by Det Obelske Familiefond and Spar Nord Fonden
文摘Methods related to experimental human pain research aim at activating different nociceptors, evoke pain from different organs and activate specific pathways and mechanisms. The different possibilities for using mechanical, electrical, thermal and chemical methods in visceral pain research are discussed with emphasis of combinations (e.g., the multimodal approach). The methods have been used widely in assessment of pain mechanisms in the esophagus and have contributed to our understanding of the symptoms reported in these patients. Hence abnormal activation and plastic changes of central pain pathways seem to play a major role in the symptoms in some patients with gastro-esophageal reflux disease and in patients with functional chest pain of esophageal origin. These findings may lead to an alternative approach for treatment in patients that does not respond to conventional medical or surgical therapy.
文摘AIM:To investigate changes in advanced glycation end products(AGEs) and their receptor(RAGE) expression in the gastrointestinal(GI) tract in type 2 diabetic rats.METHODS:Eight inherited type 2 diabetic rats GotoKakizak(GK) and ten age-matched normal rats were used in the study.From 18 wk of age,the body weight and blood glucose were measured every week and 2 wk respectively.When the rats reached 32 wk,twocentimeter segments of esophagus,duodenum,jejunum,ileum,and colon were excised and the wet weight was measured.The segments were fixed in 10% formalin,embedded in paraffin and five micron sections were cut.The layer thickness was measured in Hematoxylin and Eosin-stained slides.AGE [N epsilon-(carboxymethyl) lysine and N epsilon-(carboxyethyl)lysine] and RAGE were detected by immunohistochemistry staining and image analysis was done using Sigmascan Pro 4.0 image analysis software.RESULTS:The blood glucose concentration(mmol/L) at 18 wk age was highest in the GK group(8.88 ± 1.87 vs 6.90 ± 0.43,P < 0.001),a difference that continued to exist until the end of the experiment.The wet weight per unit length(mg/cm) increased in esophagus,jejunum and colon from the normal to the GK group(60.64 ± 9.96 vs 68.56 ± 11.69,P < 0.05 for esophagus; 87.01 ± 9.35 vs 105.29 ± 15.45,P < 0.01 for jejunum; 91.37 ± 7.25 vs 97.28 ± 10.90,P < 0.05 for colon).Histologically,the layer thickness of the GItract was higher for esophagus,jejunum and colon in the GK group [full thickness(μm):575.37 ± 69.22 vs 753.20 ± 150.41,P < 0.01 for esophagus; 813.51 ± 44.44 vs 884.81 ± 45.31,P < 0.05 for jejunum; 467.12 ± 65.92 vs 572.26 ± 93.60,P < 0.05 for colon].In esophagus,the AGE and RAGE mainly distributed in striated muscle cells and squamous epithelial cells.The AGE distribution was much stronger in the GK group compared to the normal group both in the striated muscle layer and mucosa layer(immuno-positive area/ total measuring area %:4.52 ± 0.89 vs 10.96 ± 1.34,P < 0.01 for muscle; 8.90 ± 2.62 vs 22.45 ± 1.26,P < 0.01 for mucosa).No visible difference was found for RAGE distribution between the two groups.In the intestine AGE and RAGE distributed in epithelial cells of villi and crypt.RAGE was also found in neurons in the myenteric and submucosal plexus.The intensity of AGE staining in mucosa of all segments and RAGE staining in neurons in all segments were strongest in the diabetes group.Significant difference for AGE was found in the epithelial cells of villi and crypt in duodenum(immunopositive area/total measuring area %:13.37 ± 3.51 vs 37.48 ± 8.43,P < 0.05 for villi; 0.38 ± 0.12 vs 1.87 ± 0.53,P < 0.05 for crypt) and for RAGE in neurons of all segments(e.g.,for jejunum:no staining neurons% 0 vs 0,mild 36.0 ± 5.2 vs 28.7 ± 3.5,moderate 53.2 ± 4.8 vs 55.8 ± 5.4,strong 10.7 ± 1.1 vs 15.4 ± 2.0,P < 0.05).In the colon,RAGE was primarily found in neurons in the myenteric and submucosal plexus.It was stronger in the diabetes group than in the normal group(no staining neurons% 6.2 ± 0.2 vs 0.3 ± 0.04,mild 14.9 ± 2.1 vs 17.6 ± 1.5,moderate 53.1 ± 4.6 vs 44.7 ± 4.4,strong 25.6 ± 18 vs 43.6 ± 4.0,P < 0.05).In the rectum,RAGE was primarily found in the mucosa epithelial cells.CONCLUSION:The AGE and RAGE expression was upregulated in the GI tract of GK diabetic rats and may contribute to GI dysfunction in type 2 diabetic patients.
基金Supported by "Det Obelske Familiefond" & "Spar Nord Fonden"
文摘Understanding and characterization of pain and other sensory symptoms are among the most important issues in the diagnosis and assessment of patient with gastrointestinal disorders. Methods to evoke and assess experimental pain have recently developed into a new area with the possibility for multimodal stimulation （e.g., electrical, mechanical, thermal and chemical stimulation） of different nerves and pain pathways in the human gut. Such methods mimic to a high degree the pain experienced in the clinic. Multimodal pain methods have increased our basic understanding of different peripheral receptors in the gut in health and disease. Together with advanced muscle analysis, the methods have increased our understanding of receptors sensitive to mechanical, chemical and temperature stimuli in diseases, such as systemic sclerosis and diabetes. The methods can also be used to unravel central pain mechanisms, such as those involved in allodynia, hyperalgesia and referred pain. Abnormalities in central pain mechanisms are often seen in patients with chronic gut pain and hence methods relying on multimodal pain stimulation may help to understand the symptoms in these patients. Sex differences have been observed in several diseases of the gut, and differences in central pain processing between males and females have been hypothesized using multimodal pain stimulations. Finally, multimodal methods have recently been used to gain more insight into the effect of drugs against pain in the GI tract. Hence, the multimodal methods undoubtedly represents a major step forward in the future characterization and treatment of patients with various diseases of the gut.
文摘Barrett's esophagus (BE) is characterized by intestinal metaplasia with the differentiated epithelium replaced by another type of epithelium morphologically similar to normal intestinal epithelium. The metaplasia is preceded by bile and acid reflux into the esophagus. BE is a premalignant condition associated with increased risk of esophageal cancer, especially esophageal adenocarcinoma. The Caudal-related homeodomain transcription factors Caudal-related homeodomain transcription factor CDX1 and CDX2 are expressed exclusively in the small and large intestine, playing important roles in proliferation and differentiation of intestinal epithelial cells. Ectopic expression of CDX1 and CDX2 occurs in BE. The apical sodium-dependent bile acid transporter (ASBT) is expressed primarily in terminal ileum where it is a key factor for intestinal reabsorption of bile salts. In addition to upregulation of CDX1 and CDX2, ASBT expression is up-regulated in BE. Furthermore, both CDX1/CDX2 and ASBT expressions are down-regulated in high-grade esophageal dysplasia. The alteration of the above-mentioned factors calls for attention: what is the relationship between CDXs and ASBT aberrant expression in BE? In this commentary, we discuss this issue on basis of the recent study done by Ma et al .
基金Supported by A grant from US National Institute of Health with No. 1RO1DK072616-01A2Karen Elise Jensen Fond
文摘The gastrointestinal (GI) tract is the system of organs within multi-cellular animals that takes in food, digests it to extract energy and nutrients, and expels the remaining waste. The various patterns of GI tract function are generated by the integrated behaviour of multiple tissues and cell types. A thorough study of the GI tract requires understanding of the interactions between cells, tissues and gastrointestinal organs in health and disease. This depends on knowledge, not only of numerous cellular ionic current mechanisms and signal transduction pathways, but also of large scale GI tissue structures and the special distribution of the nervous network. A unique way of coping with this explosion in complexity is mathematical and computational modelling; providing a computational framework for the multilevel modelling and simulation of the human gastrointestinal anatomy and physiology. The aim of this review is to describe the current status of biomechanical modelling work of the GI tract in humans and animals, which can be further used to integrate the physiological, anatomical and medical knowledge of the GI system. Such modelling will aid research and ensure that medical professionals benefit, through the provision of relevant and precise information about the patient's condition and GI remodelling in animal disease models. It will also improve the accuracy and efficiency of medical procedures, which could result in reduced cost for diagnosis and treatment.
