环孢素A诱发的大鼠糖尿病模型的建立及其机制的探讨

The establishment of cyclosporine induced diabetes mellitus models in rats

目的建立环孢素A诱发的大鼠糖尿病模型,通过血清胰岛素水平、胰岛素敏感指数、胰岛病理改变探讨环孢素A升高血糖作用的机制。方法雄性SD大鼠20只[(89±10)g]随机等分为两组,每组10只。环孢素A组:环孢素25 mg·kg-1·d-1;对照组:每日给予等量生理盐水,大鼠均在空腹(禁食水8 h)时灌胃给药,用药1 h后喂食。每周测量大鼠体重,每月监测大鼠空腹血糖和环孢素A的血药浓度。用药5个月后于空腹状态下将每组大鼠处死,心脏穿刺取血,4%多聚甲醛体内灌流取胰腺组织,放射免疫方法检测大鼠血清胰岛素水平,胰腺组织行病理组织学观察,应用SPSS 13.0统计软件分析对资料进行统计分析。结果给药4个月后,与环孢素A组平均血糖大于7 mmol/L,说明环孢素A诱发大鼠糖尿病模型成功。与对照组相比,环孢素组大鼠的胰岛素抵抗指数均明显升高(P<0.05),胰岛素分泌指数明显降低(P<0.05),环孢素组大鼠胰腺组织的胰导管均遭到破坏,胰岛细胞数量减少,且明显坏死、空泡化。结论环孢素A导致胰岛细胞坏死,减少胰岛素的分泌、增加胰岛素抵抗从而导致大鼠血糖升高。

ObjectiveTo establish cyclosporine A induced diabetes mellitus models in rats and to study the mechanisms of elevating blood glucose by the level of serum insulin, insulin sensitivity index and islet pathological alteration.Methods SD male rats were randomly divided into 2 groups. The rats in cyclosporine group were administrated with cyclosporine 25 mg·kg-1·d-1, while The rats in control group were administrated with equivalent distilled water everyday. Each group were taken intragastric administration on an empty stomach （fasting 8 hours） and were fed after one hour. The weight of rats were measured every week, fasting blood-glucose and blood drug level of CsA were monitored every month. The rats of each group were executed on an empty stomach after 5 months, got blood by cardiac puncture and pancreatic tissue byin vivo perfusion of 4% paraform, the level of serum insulin were tested by radio immunity method, pancreatic tissue were observed in histopathology, and SPSS 13.0 statistical analysis software was used for data analysis.Results The fasting blood glucose levels in cyclosporine group were higher than 7 mmol/L after 4 months, which indicated that cyclosporine induced diabetes mellitus model was established. After 5 months,the insulin resistance index increased significantly（P〈0.05）, insulin sensitivity index decreased significantly（P〈0.05）, pancreatic ductal of pancreatic tissues were destroyed, the number of islet cells decreased with necrosis and vacuolization in cyclosporine group than those of control group.Conclusion The hyperglycemic action of cyclosporine is effected by making islet cell necrosis, reducing insulin secretion and increasing insulin resistance.