糖尿病胃轻瘫大鼠胃窦Cajal间质细胞和缝隙连接蛋白43的变化及胰岛素的干预作用

Changes of interstitial cells of Cajal and connexin 43 expression in the gastric antrum of rats with diabetic gastroparesis: Implications for interventional effect of insulin

目的:观察糖尿病胃轻瘫(diabetic gastrop a r e s i s,D G P)模型大鼠中C a j a l间质细胞(interstitial cells of Cajal,ICC)和缝隙连接蛋白43(connexin43,Cx43)在胃窦分布的变化及胰岛素的干预作用.方法:SD大鼠随机分为糖尿病模型组、正常对照组和胰岛素干预组,用腹腔注射链脲佐菌素建立糖尿病大鼠模型,于成模后10 wk时分别处死各组大鼠,测定大鼠胃内色素残留率,用免疫组织化学法分析胃窦ICC及Cx43的表达,透射电镜(transmission electron microscope,TEM)观察ICC及缝隙连接的结构变化.结果:糖尿病组大鼠出现血糖明显升高和体质量减轻,胃内色素残留率显著增加,免疫组织化学显示环纵肌层内ICC分布减少,环形肌内Cx43的表达下降,TEM可见ICC细胞器变性、胞质溶解和缝隙连接松散等改变.胰岛素治疗可使DGP大鼠胃残留率减少,增加ICC、Cx43的数量,逆转其超微结构变化.结论:ICC和Cx43数量减少、结构破坏可能是DGP发病基础之一,而补充胰岛素可逆转糖尿病大鼠的ICC、Cx43病变从而改善胃动力障碍.

AIM： To observe the alterations of interstitial cells of Cajal（ICC） and connexin 43（Cx43） in gastric antrum tissue of a rat model of diabetic gastroparesis（DGP） and assess the interventional effect of insulin.METHODS： Sprague-Dawley rats were randomly divided into a diabetic model group, anormal control group and an insulin intervention group. Diabetes was induced by intraperitoneal injection of streptozotocin. Gastric emptying was measured,and the expression of ICC and Cx43 in the gastric antrum was analyzed by immunohistochemistry. The alterations of the ultrastructure of ICC and gap junction were observed by transmission electron microscopy（TEM） at the 10 th week after modeling.RESULTS： Blood glucose and body weight in the diabetic model group were significantly different from those in other groups.The gastric pigment remnant rate was significantly increased in the diabetic model group.Immunohistochemical staining showed that in diabetic rats, the number of ICC in the circular and longitudinal muscle layers decreased and Cx43 was lowly expressed in circular muscle layers. TEM showed organelle degeneration, cytoplasm dissolution and loosening of the structure of gap junction. Insulin could decrease the gastric pigment remnant rate, increase the number of ICC and Cx43 expression, and reverse ultrastructural changes.CONCLUSION： The decrease of ICC expression and Cx43 expression might be one of the mechanisms responsible for DGP. Insulin can increase the expression of ICC and Cx43 and thus improve gastrointestinal disorders.