| 摘要: |
| 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）。结论缬沙坦虽然对UUO大鼠肾小球、肾小管功能改善不明显,但能抑制AngⅡ的生成,可能通过下调TGF-β1的过度表达,上调HGF的表达,抑制α-SMA、FN、PAI-1的表达,从而抑制肾小管上皮细胞间充质转分化（EMT）,减少细胞外基质(ECM)沉积,达到改善RIF的作用。 |
| 关键词: 单侧输尿管梗阻 肾间质纤维化 血管紧张素Ⅱ α-平滑肌肌动蛋白 转化生长因子β1 肝细胞生长因子 |
| DOI：10.3724/SP.J.1008.2010.0278 |
| 投稿时间：2009-11-27修订日期：2010-02-09 |
| 基金项目:上海市重点学科建设项目（Y0302）. |
|
| Effects of valsartan on renal interstitium fibrosis in rats after unilateral ureteral obstruction |
| ZHOU Jian-song1, CHEN Gang2, SHEN Ye-qu2, WU Mei2, HE Li-qun2* |
| (1. Department of Nephrology, the Third Affiliated Hospital of Nantong University, Wuxi 214041, Jiangsu, China;2. Department of Nephrology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China) |
| Abstract: |
| ObjectiveTo study the effect of valsartan, an angiotensinⅡtypeⅠreceptor antagonist（AT1RA）, on renal interstitium fibrosis（RIF）in rats with unilateral ureteral obstruction （UUO）, and to discuss the possible mechanisms. MethodsThirty-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 intragastric valsartan and sodium chloride in tales doses. The serum creatinine（SCr）, blood urea nitrogen（BUN）, angiotensin-Ⅱ(AngⅡ) in blood plasma, N-acetyl-β-D-glucosaminidase（NAG）and 24 h urine β2-microglobulin（β2-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-β1）, and hepatocyte growth factor（HGF）.ResultsCompared with those in the sham-operation group, SCr, BUN, AngⅡ, NAG and β2-MG levels,and the expression of α-SMA,FN,PAI-1,and TGF-β1 in model group were significantly higher（P<0.01）. The levels of SCr,BUN,NAG and β2-MG were comparable between valsartan group and the model group（P>0.05）. The expression levels of α-SMA,FN,PAI-1,and TGF-β1 in valsartan group were significantly lower than and the expression of HGF was significantly higher than those in the model group（P<0.01）. ConclusionValsartan 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 AngⅡ, inhibiting overexpression of α-SMA,FN,PAI-1, and TGF-β1, and inducing the HGF expression. |
| Key words: unilateral ureteral obstruction renal interstitium fibrosis angiotensinⅡ alpha-smooth muscle actin transforming growth factor-beta 1 hepatocyte growth factor |
