缬沙坦对单侧输尿管梗阻大鼠肾间质纤维化的影响

目的探讨血管紧张素ⅡⅠ型受体拮抗剂(AT1RA)缬沙坦对单侧输尿管梗阻(UUO)大鼠肾间质纤维化(RIF)的影响及其可能机制。方法35只SD大鼠随机分为假手术组、模型组和缬沙坦组(n=10),建立大鼠UUO模型,于术后4周检测血清肌酐(SCr)、血尿素氮(BUN)、血浆血管紧张素Ⅱ(AngⅡ),尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)、尿β2-微球蛋白(β2-MG);取梗阻侧肾组织,以H-E、Masson染色观察肾小管间质病变,免疫组织化学染色观察α-平滑肌肌动蛋白(α-SMA)、纤维连接蛋白(FN)、纤溶酶原激活物抑制剂1(PAI-1)、转化生长因子β1(TGF-β1)及肝细胞生长因子(HGF)在肾间质的阳性染色,并进行半定量分析。结果与假手术组相比,模型组大鼠SCr、BUN、血浆AngⅡ,尿NAG、β2-MG水平以及α-SMA、FN、PAI-1、TGF-β1表达均显著升高(P<0.01)。与模型组相比,缬沙坦组大鼠SCr、BUN,尿NAG及β2-MG水平差异无统计学意义(P>0.05),但血浆AngⅡ及肾间质α-SMA、FN、PAI-1、TGF-β1表达均显著降低,HGF表达则显著增高(P<0.01)...

Effects of valsartan on renal interstitium fibrosis in rats after unilateral ureteral obstruction

Objective To study the effect of valsartan, an angiotensin Ⅱ type Ⅰ receptor antagonist(AT1RA), on renal interstitium fibrosis(RIF)in rats with unilateral ureteral obstruction (UUO), and to discuss the possible mechanisms.Methods Thirty-five Sprague-Dawley rats were randomly divided into sham-operation, model and valsartan groups.The rat UUO model was established.From the day after operation,the rats in sham-operation and model groups received intragastrie valsartan and sodium chloride in tales doses.The serum creatinine (SCr), blood urea nitrogen(BUN), angiotensin-Ⅱ (Ang Ⅱ) in blood plasma, N-acetyl-β-D-glucosaminidase(NAG)and 24 h urine β_2-microglobulin(β_2-MG)were examined 4 weeks after operation.The renal tissues of the obstructed sides were harvested; H-E staining and Masson staining were used to observe the tubulointerstitial lesions; and immunohistochemistry staining was used for semiquantitative analysis of alpha-smooth muscle actin(α-SMA), fibronectin(FN), plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-beta 1 (TGF-β_1), and hepatocyte growth factor(HGF).Results Compared with those in the sham-operation group, SCr, BUN, Ang Ⅱ , NAG and β_2-MG levels, and the expression of α-SMA, FN,PAI-1 ,and TGF-β_1 in model group were significantly higher(P.<0.01).The levels of SCr, BUN, NAG and β_2-MG were comparable between valsartan group and the model group(P>0.05).The expression levels of α-SMA,FN, PAI-1,and TGF-β_1 in valsartan group were significantly lower than and the expression of HGF was significantly higher than those in the model group(P<0.01).Conclusion Valsartan does not improve the tubular and glomerular functions,but it can inhibit production of Ang-Ⅱ.Valsartan may inhibit renal interstitial fibrosis by inhibiting renal tubule epithelial mesenchymal transdifferentiation and reducing extracellular matrix deposition through blocking up Ang Ⅱ, inhibiting overexpression of α-SMA,FN,PAI-1, and TGF-β_1, and inducing the HGF expression.