缬沙坦对单侧输尿管梗阻大鼠肾脏的保护作用

目的 :研究单侧输尿管梗阻后肾间质纤维化的发生机理及血管紧张素Ⅱ受体拮抗剂缬沙坦对其保护作用。方法 :将 2 4只大鼠随机分为假手术组即对照组、手术组和缬沙坦组 ,采用单侧输尿管梗阻 (UUO)模型 ,术后 2周观察梗阻肾组织病理改变 ,应用免疫组织化学方法检测肾间质Ⅲ型胶原 ,转化生长因子 β1(TGF - β1)和核因子 -κB(NF -κB)的表达。并应用放射免疫法检测血浆和肾组织血管紧张素Ⅱ (AngⅡ )的含量。 结果 :手术组肾间质Ⅲ型胶原 ,TGF - β1和NF -κB的表达增加 ,血浆和肾组织AngⅡ增高 ,与对照组相比有显著差异 (P <0 .0 5 )。缬沙坦组与手术组相比Ⅲ型胶原、TGF - β1、NF -κB的表达下调 ,差异显著 (P <0 .0 5 ) ,AngⅡ增加。 结论 :缬沙坦可能通过阻断AngⅡ的作用和抑制TGF - β1、NF -κB的过度表达 ,使肾间质Ⅲ型胶原沉积减少而产生保护肾脏作用。

Renoprotective Effects of Valsartan in Rats after Unilateral Ureteral Obstruction

Objective: To investigate the mechanism of renal interstitial fibrosis after unilateral ureteral obstruction and renoprotctive effect of angiotensinⅡ receptor antagonist valsartan. Methods: Twenty-four rats were randomly assigned to control group(shame operation group), operation group and valsartan(10 mg·kg -1·d -1) treatment group after unilateral ureteral obstruction. Renal tissues were examined by light microscopy at the 2nd week after operation. Immunohistochemistry was applied to measured the expression of collagenⅢ, transforming growth factor-β 1(TGF-β 1) and nuclear factor-κB (NF-κB) in the renal interstitium. Radioimmunoassay were used to quantitate level of angiotensinⅡ in renal and plasma. Results: In comparison with control group, the expression of collagen Ⅲ, TGF-β 1 and NF-κB in the interstitium of operation group were obviously increased (P<0.05). In comparison with operation group, valsartan could significantly decrease the expression of collagen Ⅲ, TGF-β 1 and NF-κB (P<0.05). Conclusion: Valsartan may protect renal by inhibitting the overexpresion of TGF-β 1, NF-κB and the deposition of collagen Ⅲ.