氯沙坦对糖尿病大鼠肾脏的保护作用

摘要

目的:观察氯沙坦对糖尿病(diabetes mellitus,DM)大鼠肾脏病变的保护作用及其机制.方法:将链脲佐菌素诱导的DM大鼠分为模型组(DM组)和氯沙坦治疗组(LOS组),另设正常对照组(NC组).氯沙坦治疗组予腹腔注射氯沙坦30 mg/(kg·d),NC组和DM组则予同体积的生理盐水.12周后收集尿样并取血,检测血糖(BG)、血肌酐、尿素氮,尿β2-微球蛋白(β2-MG)和24 h尿白蛋白排泄率(UAER),测尿和血中TNF-o和TGF-β1浓度,计算肾脏肥大指数,观察肾小球病理变化.结果:DM组尿素氮、血肌酐、UAER、血糖、β2-MG、肾重/体重明显增高(P＜0.01或P＜0.05),血、尿中TNF-α和TGF-β1浓度显著增高(P＜0.01或P＜ 0.05).氯沙坦治疗组上述指标显著低于DM模型组(P＜0.01或P＜0.05),肾脏病理明显改善.结论:氯沙坦可降低血和尿中TNF-α、TGF-β1浓度,减少尿蛋白排泄,有助于保护肾功能.%Objective To observe the protective effects of losartan on kidney of diabetic rats. Methods The Sprague Dawley rats with diabetes mellitus was induced by streptozotocin, and then were randomly divided into 3 groups: normal control group (NC group), diabetic model group (DM group) and losartan treatment group (LOS group). Rats in LOS group were treated by intraperitoneal injection of 30 mg/(kg-d) of losartan, while those in NC group and DM group were administered by the same volume of saline. 12 weeks later, the mass index of kidney, blood sugar, urea nitrogen, serum creatinine and urinary albumin excretion rate (UAER) were detected, the concentrations of TNF-a and TGF-β1 in urine and blood was determined, renal hypertrophy index was calculated, and glomerular pathological changes were observed. Results The mass index of kidney, blood sugar, urea nitrogen, serum creatinine and UAER were obviously increased (P ＜ 0.01 or P ＜ 0.05), and the concentrations of TNF-a and TGF-pl in urine and blood were notably increased in DM group (P ＜ 0.01 or P ＜ 0.05), which were significantly higher than those in in LOS group. The changes of renal pathology in LOS group were improved. Conclusion Losartan can reduce the levels of TNF-a and TGF-β1 in the blood and urine, reduce the urinary protein excretion, which contributes to the protection of renal function.