糖尿病结肠动力障碍大鼠结肠Cajal间质细胞凋亡和间隙连接蛋白43的表达

摘要

目的 探讨糖尿病结肠动力障碍大鼠结肠Cajal间质细胞(ICC)的凋亡及ICC的间隙连接蛋白43(Cx43)表达的变化在结肠动力障碍发生中的意义.方法 雄性Sprague-Dawley(SD)大鼠36只,根据体质量及血糖按随机数字表法分为正常6周组、正常10周组、糖尿病6周组、糖尿病10周组,每组9只.腹腔注射链脲佐菌素建立糖尿病模型,检测体质量、空腹血糖及胃肠推进率;HE染色观察ICC;TUNEL法检测ICC的凋亡指数;免疫组化检测ICC的c-Kit、Cx43蛋白表达.结果 (1)糖尿病组较同时间点正常组体质量下降,空腹血糖升高,胃肠推进率降低,ICC的c-Kit、Cx43蛋白表达降低(F=76.68,1397.24,18.87,137.65,87.73,P均＜0.05).(2)糖尿病10周组较糖尿病6周组空腹血糖升高,胃肠推进率降低,ICC的c-Kit、Cx43蛋白表达降低(F=76.68,1397.24,18.87,137.65,87.73,P均＜0.05).(3)糖尿病组ICC的凋亡指数与同时间点正常组相比,差异无统计学意义;糖尿病10周组与糖尿病6周组ICC的凋亡指数差异也无统计学意义(P均＞0.05).结论 ICC数量减少、Cx43蛋白表达降低可能是糖尿病结肠动力障碍的发生机制之一,且上述改变随病程发展而加重;ICC数量减少可能与ICC凋亡无关.%Objective To investigate the apoptosis and expression of connexin 43 (Cx43) of colonic interstitial cells of Cajal (ICC) in diabetic rats with colonic dysmotility,and explore their value in the development of colonic dysmotility.Methods Thirty-six male Sprague-Dawley (SD) rats were divided into 4 groups which included normal 6 weeks group,normal 10 weeks group,diabetes mellitus (DM) 6 weeks group and DM 10 weeks group (n =9) by random digital table method according to weight and fasting blood glucose (FBG).DM was induced by streptozotocin.Weight,FBG and gastrointestinal transit rate were detected.HE staining was used to examined ICC.TUNEL was used to detect apoptosis index (AI) of ICC.Immunohistochemistry was used to detect the protein expressions of c-Kit and Cx43 of ICC.Results (1)Compared with normal group,level of FBG was higher,while weight,gastrointestinal transit rate,protein expressions of c-Kit and Cx43 of ICC were lower in DM group (F =76.68,1 397.24,18.87,137.65,87.73,all P ＜ 0.05).(2) Compared with DM 6 weeks group,level of FBG was higher,while weight,gastrointestinal transit rate,protein expressions of c-Kit and Cx43 of ICC were lower in DM 10 weeks group(F =76.68,1 397.24,18.87,137.65,87.73,all P ＜0.05).(3)There was no difference between AI of ICC in DM group and normal group,and so was between DM 10 weeks group and DM 6 weeks group(all P ＞ 0.05).Conclusions Decrease of ICC and less expression of Cx43 maybe one of the mechanisms of diabetic colonic dysmotility,and the changes above become more significant with the development of disease.Decrease of ICC may be not associated with the apoptosis of ICC.