缬沙坦对糖尿病大鼠血、尿及肾组织一氧化氮、内皮素水平的影响

Effect of valsartan on nitric oxide and endothelin level of plasma,urine and renal tissues in streptozotocin induced diabetic rats

目的:研究缬沙坦对糖尿病大鼠血、尿及肾组织一氧化氮、内皮素水平的影响,探讨缬沙坦对糖尿病大鼠肾脏的保护作用及其作用机制。方法:将40只雄性Wistar大鼠随机分为3组,正常对照组(A组)8只,糖尿病对照组(B组)16只,糖尿病缬沙坦治疗组(C组)16只。腹腔注射链脲佐菌素制备糖尿病大鼠模型,缬沙坦组每日以缬沙坦24mg/kg灌胃治疗84d后,测定大鼠的肾重/体重、血肌酐、肾小球平均体积、尿白蛋白排泄率、β2微球蛋白排泄率,以及血浆、尿液及肾组织内皮素(ET)含量,测定血清、尿液、肾组织一氧化氮(NO)代谢产物二氧化氮(NO2)、三氧化氮(NO3)含量,各组间结果进行比较。结果:治疗84d后测得B组大鼠肾重/体重、肌酐清除率(Ccr)、肾小球平均体积、尿白蛋白排泄率、β2微球蛋白排泄率均高于A组,C组大鼠各指标均低于B组高于A组,B组血、尿、肾组织NO2、NO3水平均明显高于A组,且B组尿、肾组织NO2、NO3含量与尿白蛋白排泄率、Ccr、平均肾小球体积呈正相关。C组NO2、NO3含量均明显低于B组但仍高于A组。B组尿、肾组织ET水平明显高于A组,且与尿白蛋白排泄率、Ccr、平均肾小球体积呈明显正相关,C组尿及肾组织ET水平均低于B组,但其肾组织ET水平仍高于A组。结论:缬沙坦对糖尿病大鼠肾小球具有保护作用,可能是因阻碍了血管紧张素II(AngⅡ)与I型受体结合,阻断AngⅡ对NO合成及ET释放的促进作用,抑制了肾组织局部NO、ET水平。

Objective: To evaluate the protective effect of the angiotensin II type 1 (AT1) receptor antagonist, valsartan, on the kidneys of diabetic rats and study their mechanisms. Methods: Fourty male Wistar rats were randomized into A, B and C groups. Diabetes were induced by injection of streptozotocin (STZ). Group A was the normal control, group B consisted of untreated STZ-diabetics rats, group C consisted of diabetic rats treated with valsartan 24mg/kg per day for 84 days. Kidney/body weight, glomerular size, serum creatinine (Cr) urinary albumin, β2-m excretion, creatinine clearance (Ccr), nitric oxied (NO), endothelin (ET) level of plasma,urine and renal tissues were measured after 84 days. The results were compared in three groups. Results: Valsartan could correctly elevate urinary albumin, β2-m excretion, Ccr and mean glomerular volume. Urinary and renal tissues NO and ET concentratisons decreased after diabetic rats had received valsartan. Kidney/ body weight, glomerular size, serum creatinine, urinary albumin, β2-m excretion, creatinine clearance, NO and ET level of plasma, urine and renal tissues of valsartan treated group were significantly lower than those of diabetic untreated group, but still higher than those of the normal control rats. There was a significant increase in those of diabetic untreated group than those of the normal control. Conclusion: Valsartan has renal protective effect on diabetic rats, partly through down-regulating NO and ET concentrations in renal tissues expression.