缬沙坦对单侧输尿管梗阻大鼠肾脏氧化应激的影响

目的：探讨血管紧张素Ⅱ-1型受体拮抗剂（AT1Ra）缬沙坦对单侧输尿管梗阻（UUO）大鼠肾脏氧化应激的影响。方法：Wistar大鼠行左侧输尿管结扎术,分为UUO模型组（n=11）,缬沙坦治疗组（n=11）,同时设假手术对照组（n=7）。术后第14天处死各组大鼠,进行HE和Masson染色,观察肾脏病理变化;比色法测定肾组织丙二醛（MDA）和超氧化物歧化酶（SOD）含量;免疫组织化学方法测定α-平滑肌肌动蛋白（α-SMA）和转化生长因子-β1（TGF-β1）的表达。结果：UUO组与假手术组大鼠比较,肾脏病理改变加重,肾组织MDA含量明显升高（P〈0.01）,SOD含量下降（P〈0.05）,肾组织α-SMA和TGF-β1的表达显著增加（P〈0.01）。缬沙坦治疗组与UUO组大鼠比较,肾间质纤维化减轻（P〈0.05）,肾组织MDA含量降低（P〈0.05）,SOD含量升高（P〈0.05）;同时肾组织α-SMA和TGF-β1的表达降低（P〈0.05）。结论：缬沙坦可通过减少UUO组肾组织脂质过氧化物的产生,增加抗氧化酶的含量,下调TGF-β1的表达,从而显著改善UUO所致的肾间质纤维化。

Experimental Study of Valsartan in Preventing Renal Oxidative Stress of Rat Unilateral Ureteral Obstruction Model

Objective：To investigate the effects of valsartan on renal oxidative stress in rat unilateral ureteral obstruction （UUO） model. Methods： Twenty - two wistar rats underwent UUO and then received placebo （ n = 11 ） or valsartan （ 10 mg·kg^-1·d^-1 by daily gastric gavage, n = 11 ）during the 15 days from the day before surgery. Additional 7 rats were sham operated and given placebo. All the rats were killed at 14 days after surgery. Histological changes were observed by HE and Masson staining. Immunohistochemistry study was performed on renal tissue fora- smooth muscle actin （α- SMA） and transforming growth factor- β1 （TGF - β1 ）. Malondialdehyde （MDA） and superoxide dismutase （SOD） content were measured. Results： UUO group induced severe morphology changes and a significant increase in MDA content as well as immunohistochemistry of TGF- β1 ,α - SMA, but a decrease in SOD content. However, valsartan ameliorated what had mentioned. Conclusion： Valsartan can downregulate the expression of TGF- β1 and alleviate renal tubulointerstitial fibrosis in rats with UUO by reducing lipid peroxidation production and improving antioxidative enzyme contents.