胰岛素对糖尿病结肠动力障碍大鼠的干预效果及其机制

摘要

Objective To explore the effect and mechanism of intervention with insulin on diabetic rats with colonic dysmotility. Methods Thirty-six male SD rats were randomly divided into normal group ,diabetes mellitus ( DM) group,insulin 1 group and insulin 2 group,with 9 rate in each group.Modeling was conducted using streptozocin intravenously in the DM group ,insulin 1 group and insulin 2 group.Subcutaneous injection of insulin was performed in the insulin 1 group and insulin 2 group after successful modeling and after 6 weeks of successful modeling respectively.No treatment was performed in the normal group or DM group.At the 10th week after successful modeling,the FBG level,gastrointestinal transit rate and serum insulin level were detected in the rats of each group.The colon tissues were removed after rats sacrifice ,then the changes in the smooth muscle of colon were observed under microscope.The apoptosis index ( AI) and apoptosis-related protein expression levels[including B-cell lymphoma-2(Bcl-2),Bcl-2 associated X(Bax) protein and cysteinyl aspartate specific proteinase(Caspase)-3 protein] were measured in the smooth muscle cells (SMC) of colon.Results Compared to the normal group, thinner colon smooth muscle and less SMC were observed in the rats of the DM group ,and the same phenomenon in milder degree was found in the insulin 1 group and insulin 2 group.The FBG,Caspase-3 protein expression levels and AI of colon SMC increased but serum insulin level decreased in the order of the normal group ,the insulin 1 group,the insulin 2 group and the DM group(P<0.05),but no significant difference was found between the normal group and the insulin 1 group(P>0.05).The Bax protein expression levels increased and Bcl-2 protein expression levels decreased in the colon SMC in the order of the normal group ,the insulin 1 group,the insulin 2 group and the DM group(P<0.01).The gastrointestinal transit rate of the normal group or the insulin 1 group was higher than that of the insulin 2 group or the DM group(P<0.05),but no significant difference was found between the normal group and the insulin 1 group or between the insulin 2 group and the DM group(P>0.05).Conclusion Intervention with insulin can improve the colonic dysmotility probably by significant anti-apoptotic and hypoglycemic effects.And early intervention has significant affects.%目的 探讨胰岛素对糖尿病结肠动力障碍大鼠的干预效果及其作用机制.方法 36只雄性SD大鼠随机分为正常组、糖尿病组(DM组)、胰岛素1组、胰岛素2组各9只.DM组、胰岛素1组、胰岛素2组大鼠给予静脉注射链脲菌素建模,分别在造模成功后及造模成功6周后给予胰岛素1组、胰岛素2组大鼠皮下注射胰岛素,而正常组及DM组无处理.造模成功后第10周检测各组大鼠的FBG、胃肠推进率及血清胰岛素水平;处死大鼠后取结肠组织,镜下观察结肠平滑肌变化,并检测结肠平滑肌细胞(SMC)的凋亡指数(AI)及凋亡相关蛋白[B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2相关X蛋白(Bax)及半胱-天冬氨酸蛋白酶(Caspase)-3蛋白]的表达水平.结果 与正常组相比,DM组大鼠结肠平滑肌变薄,SMC数目减少;胰岛素1、2组大鼠的上述情况较DM组减轻.正常组、胰岛素1组、胰岛素2组、DM组大鼠的FBG、结肠SMC的Caspase-3蛋白表达水平及AI依次增高而血清胰岛素依次降低(P<0.05),但正常组与胰岛素1组比较,差异无统计学意义(P>0.05);正常组、胰岛素1组、胰岛素2组、DM组大鼠结肠SMC的Bax蛋白表达水平依次升高而Bcl-2蛋白表达水平依次降低(P<0.01);正常组、胰岛素1组的胃肠推进率高于胰岛素2组、DM组(P<0.05),但正常组与胰岛素1组间、胰岛素2组与DM组间比较,差异无统计学意义(P>0.05).结论 胰岛素干预可能通过抗凋亡及降血糖作用改善结肠动力障碍,且早期干预效果显著.