缬沙坦及苯那普利对5/6肾切除大鼠血清瘦素水平及肾小球硬化的影响  

Effects of valsartan and benazepril on serum leptin levels and glomerulosclerosis in rats with 5/6 nephrectomy

作　　者：杨利才[1] 张道友[1] 朱新俭[1] 汪裕伟[1] 徐海红[1] 

机构地区：[1]皖南医学院第一附属医院弋矶山医院肾内科,安徽芜湖241001

出　　处：《皖南医学院学报》2017年第3期211-214,共4页Journal of Wannan Medical College

摘　　要：目的:观察缬沙坦及苯那普利对5/6肾切除大鼠血清瘦素(leptin)水平及其肾小球硬化的影响,探讨其作用机制。方法:选用SD雄性大鼠30只,其中24只通过5/6肾切除法制造慢性肾功能衰竭(CRF)模型,术后2周随机分为模型组、缬沙坦组及苯那普利组,另6只为假手术组。术后第6周末各组大鼠进行肾功能(Scr、BUN)及血清瘦素的测定;处死大鼠,取出肾脏进行病理组织形态学观察,测定肾小球硬化指数(GSI),采用免疫组织化学方法检测肾脏转化生长因子β_1(TGF-β_1)、Ⅳ型胶原(ColⅣ)及纤维连接蛋白(FN)表达。结果:模型组瘦素明显升高,与GSI、TGF-β_1、ColⅣ及FN呈正相关(r值分别为0.871、0.951、0.919、0.913)。与模型组相比,缬沙坦组及苯那普利组血清瘦素水平明显降低,肾功能及GSI明显改善,肾脏转化生长因子TGF-β_1、ColⅣ及FN表达减少(P<0.01)。结论:慢性肾衰存在高瘦素血症,阻断RAS可通过降低瘦素水平改善肾小球硬化。Objective：To observe the changes of serum leptin levels and the relationship with glomerulosclerosis as well as the effects of valsartan and benazepril on the serum leptin levels in model rats of 5/6 nephrectomy for identifying the mechanisms of serum leptin levels and glomerulosclerosis.Methods：A total of 30 male SD rats were selected,in which 6 were included as sham operation group,and 24 were undergone 5/6 nephrectomy to develop the chronic renal failure（CRF） model and randomized into model group,valsartan group and benazepril group 2 weeks after modeling.By the sixth week after operation,rats in each group were measured for the blood urea nitrogen（BUN）,serum creatinine（Scr） and leptin levels.Then the rats were sacrificed to take the kidneys for histological observation on the pathological changes and determination of glomerulosclerosis index（GSI）.Immunohistochemistry was used to detect the expression of transforming growth factorβ1（TGF-β1）protein,fibronectin（FN） and collagen Ⅳ（Col Ⅳ） in the glomeruli.Results：Serum leptin level was significantly elevated and positively correlated with GSI,TGF-β1,Col Ⅳ and FN in rats in the model group.Rats treated with valsartan or benazepril had significantly decreased serum leptin levels,ameliorated renal function and GSI,yet evidently down-regulated expression of TGF-β1,FN and ColⅣ in glomeruli compared to the models（P〈0.01）.Conclusion：Hyperleptinemia is commonly concomitant with chronic renal failure,however,glomerulosclerosis may be improved by reduceing the leptin levels via blocking renin-angiotensin system（RAS）.

关 键 词：慢性肾功能衰竭 瘦素 血管紧张素受体阻断剂 血管紧张素转化酶抑制剂 转化生长因子β1 

分 类 号：R692.5[医药卫生—泌尿科学]