糖尿病结肠动力障碍时Cajal间质细胞和干细胞因子的变化以及胰岛素的干预效应  

Alterations of Interstitial Cells of Cajal and Stem Cell Factor in Diabetic Colon Dysmotility and the Interventional Effect of Insulin

作　　者：林琳[1] 徐丽明[1] 罗云[1] 吴高珏[1] 汤玉蓉[1] 张红杰[1] 李学良[1] 

机构地区：[1]南京医科大学第一附属医院消化科,210029

出　　处：《胃肠病学》2008年第4期200-204,共5页Chinese Journal of Gastroenterology

基　　金：国家重点基础研究发展计划(2006CB503908)资助

摘　　要：背景:Cajal间质细胞(ICC)异常可能是糖尿病胃肠动力障碍的重要原因之一。目的:观察糖尿病结肠慢传输型动力障碍大鼠ICC及其Kit受体配体干细胞因子(SCF)的变化,以及胰岛素干预对结肠动力障碍和ICC的影响。方法:雄性Sprague-Dawley大鼠分为正常对照组、糖尿病模型组和不同剂量胰岛素(每天8、12、16U/kg)干预组。于成模第6、8、10周时分批处死各组大鼠,以免疫组化染色、蛋白质印迹法和电子显微镜观察近端结肠组织ICC的变化,以酶联免疫吸附测定(ELISA)和荧光定量聚合酶链反应(qPCR)检测血清和结肠组织SCF的表达。结果:糖尿病模型大鼠胃肠推进率显著降低,近端结肠组织ICC数量减少,超微结构破坏,结肠组织可溶型SCF(S-SCF)mRNA表达和血清S-SCF、胰岛素水平降低。小剂量胰岛素干预可显著改善糖尿病大鼠的胃肠推进率,增加ICC数量,逆转其超微结构改变;中、大剂量胰岛素干预则无明显作用。结论:糖尿病大鼠胰岛素分泌减少,使S-SCF表达降低,引起结肠组织ICC数量减少,结构破坏,可能是结肠慢传输型动力障碍的发生基础之一。小剂量胰岛素可改善糖尿病大鼠的ICC病变和结肠动力障碍。Abnormality of interstitial cells of Cajal （ICC） is suggested to be one of the important factors in diabetic gastrointestinal dysmotility. Aims： To observe the changes of ICC and its Kit receptor ligand/stem cell factor （SCF） in diabetic rats with slow transit colon dysmotility, and to investigate the influence of insulin intervention on colon dysmotility and ICC. Methods： Male Sprague-Dawley rats were divided into normal control group, diabetic model group, and three insulin intervention groups treated with different dosages of insulin （8, 12 and 16 U/kg per day）. The animals were sacrificed at the 6th, 8th and 10th week after modeling. The alterations of ICC in proximal colonic tissue were analyzed by immunohistochemistry, Western blotting and electron microscopy, and the expression of serum and colonic SCF was assessed by enzyme-linked immunosorbent assay （ELISA） and fluorescent quantitative polymerase chain reaction （qPCR）. Results： Gastrointestinal transit rate in the diabetic model rats decreased significantly, and the amount of ICC in proximal colonic tissue was reduced with destruction of uhrastructure. The serum and colonic expression of soluble SCF （S-SCF） and serum insulin level also decreased significantly in the diabetic model rats. Low-dosage insulin intervention could accelerate the gastrointestinal transit, increase the amount of ICC and reverse its ultrastructural changes, while no significant improvement was observed in moderate- and high-dosage insulin intervention groups. Conclusions： Decline of serum insulin level and the subsequent lowering of S-SCF and decrease of amount of ICC in colonic tissue with destruction in uhrastructure might be one of the underlying mechanisms of slow transit colon dysmotility in diabetic rats. Low-dosage insulin can improve the abnormality of ICC and colon dysmotility.

关 键 词：糖尿病 实验性 结肠动力障碍 CAJAL间质细胞 干细胞因子 胰岛素 大鼠 Sprague-Dawley 

分 类 号：R587.2[医药卫生—内分泌] R574[医药卫生—内科学]