厄贝沙坦对单侧输尿管梗阻大鼠肾间质纤维化的抑制作用  

Effect of irbesatan on inhibiting renal interstitial fibrosis in rats with unilateral ureteral obstruction

作　　者：孙蔚楠[1] 阎磊[1] 邵凤民[1] 

机构地区：[1]郑州大学人民医院河南省人民医院肾内科,郑州450003

出　　处：《中华实用诊断与治疗杂志》2015年第12期1157-1159,共3页Journal of Chinese Practical Diagnosis and Therapy

基　　金：河南省科技攻关计划项目(122102310074);河南省医学科技攻关计划项目(201203129)

摘　　要：目的探讨厄贝沙坦对单侧输尿管梗阻(unilateral ureteral obstruction,UUO)大鼠肾间质纤维化的抑制作用及其可能机制。方法 25只SD大鼠随机分为假手术组5只、UUO组和UUO厄贝沙坦治疗组(厄贝沙坦组)各10只,UUO组和厄贝沙坦组建立UUO大鼠模型,术后厄贝沙坦组给予厄贝沙坦50mg/(kg·d)灌胃,假手术组及UUO组大鼠以等量蒸馏水灌胃。术后第14天,取大鼠肾组织行Masson染色,观察肾脏组织病理改变并进行肾间质纤维化评分,采用Western blot法检测肾组织钙黏蛋白(E-cadherin)、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)、β-链蛋白(β-catenin)、Snail1蛋白表达情况。结果术后第14天,假手术组大鼠肾组织形态结构基本正常;UUO组大鼠出现明显肾小管萎缩,间质炎细胞浸润,间质增宽及小管间质纤维化表现;厄贝沙坦组大鼠肾组织病理学改变较UUO组明显减轻;UUO组大鼠肾间质纤维化评分(2.35±0.21)高于厄贝沙坦组(1.58±0.34)和假手术组(0.23±0.16)(P<0.05),厄贝沙坦组高于假手术组(P<0.05);术后第14天,UUO组大鼠肾组织E-cadherin表达水平(0.41±0.21)低于假手术组(1.31±0.13)和厄贝沙坦组(0.72±0.16),α-SMA、β-catenin和Snail1表达水平(1.50±0.23、1.47±0.14、1.25±0.06)高于假手术组(0.46±0.19、0.51±0.11、0.29±0.17)和厄贝沙坦组(0.86±0.26、0.77±0.21、0.68±0.24)(P<0.05);厄贝沙坦组大鼠肾组织E-cadherin表达水平低于假手术组,α-SMA、β-catenin和Snail1蛋白表达水平高于假手术组(P<0.05)。结论厄贝沙坦可部分抑制UUO大鼠肾间质纤维化,其机制可能与抑制β-catenin/Snail1通路有关。Objective To investigate the effect of irbesatan on inhibiting renal interstitial fibrosis rats with in unilateral ureteral obstruction （UUO） and its possible mechanism. Methods Twenty-five SD rats were randomly divided into three groups： sham-operation group （n= 5）, UUO group （n= 10） and irbesatan group （n= 10）. UUO models were established in UUO group and irbesatan group. Irbesatan group received gavage with irbesatan at a dose of 50 mg/kg per day, and sham-operation group and UUO group received gavage with the same volume of distilled water. The renal tissue was obtained for Masson staining to observe the pathological changes and was scored the renal interstitial fibrosis by day 14 after operation. The expressions of E-cadherin, s-smooth muscle actin （α-SMA）, β-catenin and Snaill were detected by Western blot method. Results By day 14 after operation, sham-operation group showed normal glomerular and tubulointerstitial morphology. UUO group showed obvious tubular atrophy, inflammatory cell infiltration and tubulointerstitial fibrosis. Irbesatan group showed slight histopathologic changes in renal tissue. The score of renal interstitial fibrosis was significantly higher in UUO group （2.35±0.21） than that in irbesatan group （1.58±0.34） and sham-operation group （0.23 ± 0. 16） （P〈（0.05）, and was significantly higher in irbesatan group than that in sham-operation group （P〈0.05）. By day 14 after operation, the level of E-cadherin was significantly lower in UUO group （0.41±0.21） than that in sham-operation group （ 1.31±0. 13） and irbesatan group （0.72±0. 16）, and the levels of α-SMA, β-catenin and Snail1 were significantly higher in UUO group （1. 50±0. 23, 1. 47±0. 14, 1. 25±0.06） than those in sham-operation group （0.46±0.19, 0. 51±0.11, 0. 29±0.17） and irbesatan group （0.86±0.26, 0. 77±0. 21, 0.68±0.24） （P〈0.05）. The level of E-cadherin was lower and the levels of α-SMA, β-catenin and Snail1 were higher in irbesatan g

关 键 词：肾间质纤维化 厄贝沙坦 上皮细胞-间充质转分化 Β-链蛋白 SNAIL1 大鼠 

分 类 号：R692[医药卫生—泌尿科学]