依贝沙坦对单侧输尿管梗阻小鼠肾脏整合素连接激酶表达的影响及意义  

Influence of irbesartan on the expression of integrin-linked kinase and its relationship with epithelial mesenchymal transition in mice with unilateral ureteral obstruction

作　　者：夏慧玲[1] 刘必成[1] 张晓良[1] 刘殿阁[1] 吴冀宁[1] 张建东[1] 弓玉祥[1] 

机构地区：[1]东南大学附属中大医院肾脏病研究所,南京210009

出　　处：《中华肾脏病杂志》2007年第6期382-387,共6页Chinese Journal of Nephrology

基　　金：国家自然科学基金（30471732）;江苏省“135”工程医学重点人才基金（RC2002072）

摘　　要：目的研究依贝沙坦（Irb）对单侧输尿管梗阻（UUO）小鼠肾脏整合素连接激酶（ILK）表达的影响,并探讨其与肾小管上皮间充质转化的关系。方法将雄性CD-1小鼠随机分为假手术对照组（C,n=20）、UUO组（UUO,n=40）和Irb治疗组（UUO＋Irb,n=40）,分别于术后1、3、7和14d处死小鼠。Masson染色观察肾间质纤维化。免疫组化检测小鼠肾组织ILK、上皮细胞钙黏蛋白（E-cadherin）和α平滑肌肌动蛋白（α-SMA）表达。Western印迹观察小鼠肾组织ILK蛋白表达。荧光实时定量PCR（real-time PCR）检测ILK、E-cadherin、α-SMA和纤连蛋白（FN）mRNA表达。结果与C组相比,UUO组术后1d ILK mRNA及蛋白表达均增高;术后3d FN mRNA表达上调,E-cadherin mRNA及蛋白表达明显减少,α-SMA mRNA及蛋白表达显著增加。与UUO组相同时间点比较,Irb治疗组ILK、FN及α-SMA表达均被显著抑制（P均＜0．05）;E-cadherin表达则增高（P＜0．01）。ILK蛋白表达与α-SMA蛋白表达呈正相关（r =0．707,P＜0．01）,与E-cadherin蛋白表达呈负相关（r=-0．919,P＜0．01）。结论Irb能减轻肾脏纤维化,抑制肾小管上皮细胞转分化,这可能与其抑制肾小管细胞ILK表达有关。Objective To investigate the influence of irbesartan on the expression of integrin-linked kinase （ILK） and its relationship with epithelial-mesenchymal transition （EMT） in mice with unilateral ureteral obstruction （UUO）. Methods Mice were randomly divided into three groups： sham operation （C, n=20）, UUO （n=40） and UUO with irbesartan treatment （UUO＋ Irb, n =40）, Animals were sacrificed at day 1, 3, 7 and 14 respectively after the surgery. Tubulointerstitial fibrosis （TIF） was graded according to Masson staining, The expression of ILK was examined by immunohistochemistry, Western blot and real time PCR, respectively, mRNA expression of FN was measured by real-time PCR, Expression of α-SMA and E-cadherin was detected by immunohistochemistry and real-time PCR. Results The expression levels of ILK mRNA and protein were significantly increased in UUO group, which was significantly decreased by treatment with Irb （P 〈 0.01）. The expression of α-SMA and the mRNA level of FN were significantly increased, while E-cadherin was decreased in mice with UUO at day 3 after the surgery. Treatment with Irb significantly abrogated such effects （P 〈 0.01 ）, The protein expression of ILK was positively correlated with α-SMA, but negatively with E-cadherin. Conclusions Irbesartan attenuates renal tubulointerstitial fibrosis in UUO mice, which may be related to the inhibition of ILK expression and the subsequent prevention of tubular epithelial-mesenchymal transition.

关 键 词：依贝沙坦 输尿管梗阻 肾小管 整合素连接激酶 上皮细胞转分化 纤维化 

分 类 号：R686[医药卫生—骨科学]