氨基胍对糖尿病大鼠肾脏保护作用的实验研究

Role of aminoguanidine in protecting the kidney function of streptozocin-induced diabetic rats

目的:研究糖尿病大鼠肾脏蛋白激酶C(protein kinase C,PKC)活性变化,探讨氨基胍对糖尿病大鼠肾脏的保护作用及其机制。方法:将60只雄性Wistar大鼠随机分为3组,正常对照组(A)、糖尿病对照组(B)及糖尿病氨基胍治疗组(C),每组各20只,C组大鼠给予氨基胍治疗24周,分别测定治疗8、24周时大鼠的体重、血糖、糖化血红蛋白(HbA1c)、肾功能、尿蛋白、PKC活性和肾小球总二酰基甘油(DAG)的含量,比较各组治疗结果。结果:治疗82、4周后,测得B组大鼠血糖、HbA1c、肌酐清除率(Ccr)、尿蛋白、肾小球PKC活性和肾小球总DAG的含量均升高,C组糖尿病大鼠的血糖、HbA1c及体重变化无显著性差异,但C组糖尿病大鼠的Ccr、尿蛋白2、4周时肾小球PKC活性和肾小球总DAG的含量与B组大鼠对照明显下降。结论:糖尿病大鼠肾脏PKC活性升高,氨基胍可下调PKC活性并可能是一种新的PKC抑制剂,氨基胍阻止或延缓糖尿病肾脏损害可能涉及多种机制,通过抑制PKC活性是其机制之一。

Objective： To explore the aheration of protein kinase C（PKC） activity and the effect of aminoguanidine （AG） on diabetic glomerulopathy in streptozocin （STZ）-induced diabetic rats. Methods： A total of 60 male Wistar rats were randomized into normal control, diabetes control and AG treatment group. Blood glucose, HbA1 c, serum creatinine（Cr）, urinary albumin, creatinine clearance rate （Ccr）, PKC activity and DAG level of glomerular were measured 8 and 24 weeks after the treatment and compared the results from other groups. Results： The level of blood glucose, HbA1c, urinary albumin, the PKC activity, the Ccr and the DAG level of glomerular were all significantly increased in diabetic rats. AG had no effect on the alteration of blood glucose, HbA1c and weight in diabetic rats, but decreased the level of urinary albumin, the PKC activity, the Ccr and the DAG level of glomerular. Conclusion： The rise of PKC activity plays an important role in the development of diabetic nephropathy. AG could reduce the PKC activity and may be a novel inhibitor of protein kinase C.