目的：探讨糖耐康干预2型糖尿病大鼠（ZDF）胰岛β细胞凋亡的作用及机制。方法：6只雄性ZDF（fa/+）大鼠设为正常对照组，雄性ZDF（fa/fa）大鼠30只设为2型糖尿病成模组。根据体质量及随机血糖将成模组大鼠随机分为5组，即模型组、二甲双胍组、糖耐康高、中、低剂量组。给药前测大鼠空腹血糖值及血清胰岛素值；给药6周再次检测大鼠空腹血糖值及血清胰岛素值并进行比较。采用HE染色观察胰岛形态结构的改变；采用TUNEL法检测各组大鼠胰腺组织中胰岛β细胞凋亡情况；免疫组织法观察细胞死亡信号转导效应酶Caspase-3在胰岛中表达情况。结果：给药6周后，糖耐康高、中、低剂量组均可显著改善ZDF大鼠空腹血糖（P<0.01）；糖耐康高、中、低剂量组血清胰岛素值较模型组均有所升高，其中，高、低剂量组有显著性差异（P<0.05）；给药组胰岛素抵抗指数较模型组均有所下降，其中，糖耐康高剂量组及二甲双胍组有极显著性差异（P<0.01）。HE染色显示给药组的胰岛细胞形态、结构较模型组有所改善。TUNEL结果显示ZDF（fa/fa）大鼠胰腺组织内均可见胰岛细胞凋亡改变，与模型比，给药组TUNEL阳性表达率均显著性减少（P<0.05）。免疫组化结果显示给药组Caspase-3蛋白表达下降（P<0.05）。结论：糖耐康能有效降低ZDF大鼠胰岛β细胞的凋亡，即对胰岛β细胞有一定的保护作用。

This study aimed to investigate the anti-apoptotic effects of Tangnaikang(TNK)on islet β cells in Zucker diabetic fatty(ZDF)rats.Six male fa/+ ZDF rats were took as the control group,while other thirty male fa/fa ZDF rats were divided into five groups at random:the model group,the metformin group,the high-, mediumand low-dose TNK groups,depending on their body weight and random blood glucose.Prior to the administration,fasting blood glucose and fasting insulin were measured by drawing blood with inner canthusl.Materials were prepared when administered for six weeks.Fasting blood glucose and fasting insulin were detected again.When the sections of the rat pancreatic tissue were embedded,the morphological changes of the islet were observed via HE staining,and the apoptosis of islet β cell were observed using TUNEL.Positive expression of Caspase-3,the transduction enzyme of cell death signal,was tested by immunohistochemical method.It was found that the fasting blood glucose of the(fa/fa)ZDF rats in the high-,medium- and low-dose TNK group was significantly improved after administration(P<0.01).The serum insulin of rats in the high-,medium- and low-dose TNK group arised compared with the model group,while the high- and low-dose TNK group showed differences in a statistical sense.Compared with the model group,the HOMA-IR of all the treatment group decreased,while significant difference was presented between the high-dose TNK group and the metformin group.HE staining showed that the morphology of the islet β cell of the rats in all the treatment group was improved.The results of TUNEL showed significantly apoptotic changes on islet β cell of the fa/fa ZDF rats.Compared with the model group,the positive expression of TUNEL in the metformin group and the high-dose TNK group were significantly reduced(P<0.05).The result of immunohistochemistry method showed that the protein levels of Caspase-3 in the metformin group and the high-dose TNK group decreased(P<0.05).In conclusion,it was demonstrated that TNK effectively reduced the apoptosis of islet β cells in fa/fa ZDF rats,which presented a protective effect.

科学技术部国家“十二五”科技支撑计划课题（2014BAI10B04）：中药干预糖调节受损临床疗效评价研究，负责人：刘铜华。