蛋白激酶 C-β抑制剂 LY333531对1型糖尿病大鼠肾功能的影响∗

摘要

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 glucose,creati-nine 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-βinhibitor LY333531 may be used therapeu-tically to improve creatinine clearance rate and proteinuria of type 1 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。