蛋白激酶C-β抑制剂LY333531对1型糖尿病大鼠肾功能的影响

Effects of Protein Kinase C-βInhibitor LY333531 on Renal Function in Diabetic Rats

目的:观察蛋白激酶C(PKC)-β抑制剂LY333531对1型糖尿病大鼠肾功能的保护作用。方法:27只SD大鼠随机分为正常对照组、糖尿病组和LY组,每组各9只。后两组采用一次性尾静脉注射60mg/kg链脲佐菌素(STZ)成功构建1型糖尿病模型。LY组大鼠给予PKC-β抑制剂LY333531(10mg/kg/天)灌胃治疗8周。抽取各组大鼠颈动脉血并留取24h尿液,测量血糖、内生肌酐清除率和24h尿蛋白。之后处死各组大鼠,摘取肾脏称重并计算肾重/体重。统计学分析各组上述指标的差异。结果:与正常对照组比较,糖尿病组和LY组大鼠的体重均明显减轻,而肾重、肾重/体重、血糖及24h尿蛋白均显著升高(P<0.05);LY组大鼠的肾重/体重、内生肌酐清除率及24h尿蛋白水平均低于糖尿病组(P<0.05),两组肾重、体重和血糖差异无统计学意义(P>0.05)。结论:PKC-β抑制剂LY333531有利于改善1型糖尿病大鼠内生肌酐清除率和减少蛋白尿的产生。

Objective： To investigate the renoprotective effects of protein kinase C （PKC）-β inhibitor LY333531 in type 1 diabetic rats. Method： Twenty-seven Sprague-Dawley （SD） rats were randomized into three groups： normal control group, diabetic group and diabetic with LY333531 treatment group. Both of diabetic group and diabetic with LY333531 treatment group rats were injected intraperitoneally with 60 mg/kg streptozotocin （STZ） to induce type 1 diabetes. The LY treatment group rats were treated with LY333531 （10mg/kg/day） for eight weeks by gavage. After carotid artery blood and 24-hour urine of each group collected, blood glucose9 creatinine clearance rate and 24-hour urine protein levels were measured. Meanwhile body weight and kidney weight was examined. All the indicators in three groups were analyzed by using statistics. Results： Both diabetic group and LY treatment group rats had higher kidney weight, kidney weight/body weight, blood glucose and 24-hour urine protein levels than normal control group （P〈0.05）. But body weight in diabetic group and LY treatment group rats were lighter than normal control group （P〈0.05）. The kidney weight/body weight, creatinine clearance rate and 24-hour urine protein levels of LY treatment group rats were significantly decreased compared with diabetic group （P〈0. 05）. Besides, there was no significant difference in kidney weight, body weight and blood glucose between LY treatment group and diabetic group （P〈0.05）. Conclusion： The PKC-J3 inhibitor LY333531 may be used therapeutically to improve creatinine clearance rate and proteinuria of type 1 diabetic rats.