血管紧张素Ⅱ受体拮抗剂伊贝沙坦对糖尿病大鼠肾脏的保护作用

目的:探讨血管紧张素Ⅱ受体拮抗剂伊贝沙坦对糖尿病大鼠肾脏的保护作用及其相关机制。方法:将40只Wistar大鼠随机分为正常对照组、糖尿病组、伊贝沙坦组和卡托普利组4组,每组10只。12周终止实验处死大鼠,取血、尿和肾脏标本,测定尿量、体重、肾重/体重、血糖、糖化血红蛋白(HbAlc)、内生肌酐清除率(Ccr)、尿白蛋白排泄率(UAR)和尿β₂-微球蛋白(β₂-MG);测定血液、尿液和肾组织的一氧化氮(NO)和内皮素-1(ET-1)含量。结果:12周终止实验时,糖尿病各组大鼠的尿量、肾重/体重、血糖、HbAlc、UAR、β₂-MG、Ccr、血液、尿液和肾脏组织的NO和ET-1水平均明显高于或大于正常组,体重明显低于正常组(P<0.01);伊贝沙坦组和卡托普利组大鼠的血液、尿液和肾脏组织的NO和ET-1水平、UAR、β₂-MG、Ccr明显少于糖尿病组(P<0.05);血液、尿液和肾组织NO和ET-1水平与尿白蛋白排泄率、内生肌酐清除率和β₂微球蛋白呈正相关。结论:伊贝沙坦能延缓糖尿病大鼠肾脏功能损害的进展,其机制可能与伊贝沙坦不同程度地抑制糖尿病大鼠NO和ET-1的产生有关。

The protective effects of angiotensin Ⅱreceptor blocker irbesartan on kidney function in diabetic rats

AIM: To investigate the effects and mechanisms of irbesartan, one of the angiotensin Ⅱreceptor blockers, on kidney function in diabetic rats. METHODS: Forty adult male Wistar rats were randomly divided into four groups: control group, diabetes group, irbesartan group and captopril group. At the end of 12 weeks, the rats were sacrificed. Urine volume, body weight, kidney weight/body weight, plasma, glucose, glycosylated hemoglobin (HbA₁c), urinary β₂-microglobulin (β₂-MG) excretion, urinary albumin excretion rate (UAR), creatinine clearance (Ccr) were measured. Nitric oxide (NO) and endothelin-1 (ET-1) levels in plasma, urinary and renal tissues were determined. RESULTS: Urine volume, kidney weight/body weight, plasma glucose, HbA1C, UAR, Ccr, urinary β₂-MG excretion, NO and ET-1 levels of urinary, blood and renal tissue in diabetic rats were significantly higher than those of normal controls ( P<0.01). UAR, Ccr, urinary β₂-MG excretion, ET-1 and NO levels of urinary and renal tissue in rats of irbesartan and captopril groups were significantly lower than those of DM rats ( P<0.01). There were positive relationships among the levels of plasma, urinary, renal tissue ET-1, NO and UAR, Ccr and urinary β₂-MG excretion. CONCLUSION: Irbesartan could prevent from the injury of renal function in STZ-induced diabetic rats. And it maybe one of the most importan mechanisms that irbesartan could reduce the NO and ET-1 levels in STZ-induced diabetic rats.