MicroRNA-21在单侧输尿管梗阻大鼠间质纤维化肾脏组织中的表达及意义  

Expression and significance of MicroRNA-21 in renal tubulointerstitial fibrosis tissues of UUO rats

作　　者：雷学智[1] 徐小龙[1] 胡建敏[1] 孙光曦[1] 李民[1] 郭颖[1] 陈桦[1] 张焕标 赵明[1] 

机构地区：[1]南方医科大学珠江医院器官移植科,广州510282

出　　处：《重庆医学》2015年第24期3319-3322,共4页Chongqing medicine

基　　金：国家自然科学基金资助项目(81170696)

摘　　要：目的观察MicroRNA-21(miRNA-21)在单侧输尿管梗阻(UUO)大鼠肾脏组织中的表达,初步探讨其在转化生长因子-β1(TGF-β1)/Smad3致大鼠肾间质纤维化(RIF)信号通路中的机制。方法选择20只SD雄性大鼠,分为UUO组和假手术组(Sham组),分别于建模后第3天、第7天各采集每组5只大鼠肾脏组织,应用实时荧光定量PCR(Real-time qPCR)方法检测肾脏组织中miRNA-21的表达变化,采用Masson染色、苏木素-伊红(HE)染色和免疫组织化学技术评价肾组织纤维化,使用免疫组织化学检测肾脏组织中TGF-β1、Smad3、Ⅰ型胶原蛋白(Col-Ⅰ)和α平滑肌肌动蛋白(α-SMA)表达情况。结果建模后第3天和第7天UUO组肾脏组织中miRNA-21与Sham组比较均升高(P<0.01),7dUUO组肾组织中miRNA-21与3dUUO组相比升高(P<0.01)。建模后3、7dUUO组Masson染色纤维化评分、TGF-β1、Samd3、α-SMA及Col-Ⅰ蛋白阳性表达面积较Sham组升高(P<0.01),以上指标7dUUO组较3dUUO组比较表达增强(P<0.01)。UUO组肾组织中miRNA-21的表达与肾间质纤维化评分正相关(r=0.888,P<0.01);肾组织miRNA-21与TGF-β1、Smad3、Col-Ⅰ、α-SMA蛋白表达呈正相关(r=0.799、0.849、0.882、0.896,P<0.01)。结论 UUO大鼠肾组织中miRNA-21在建模后表达上调,且间质纤维化程度越重表达越高,TGF-β1/Smad3信号通路可能是通过上调miRNA-21从而介导大鼠肾间质纤维化。Objective To observe the expression of MicroRNA-21（miRNA-21）in kidney tissue of unilateral ureteral obstruc- tion （UUO） rats and explore mechanisms of miRNA-21 involved in TGF-β1/Smad3 signaling pathway in renal interstitial fibrosis （RIF）. Methods Totally Z0 adult male SD rats were divided into UUO group and Sham operation group. The left ureter of rats in UUO group were ligated,and the rats in sham group were dissociated left ureter only,but not to be obstructed. The left kidney tis- sue was collected at the 3rd.Tth days after surgery. Real-time quantitative PCR analysed the expression of miRNA-21. Masson stai- ning,HE staining and immunohislochemistry staining were used to evaluate the degree of RIF. The expression of transforming growth factor-l]1 （TGF-131） .Smad3, ^-smooth muscle actin （a-SMA） .and collagen I （Col- I ）were examined by immunohislochemis- try staining. Results The expression of miRNA-21 in kidney tissue was higher at 3rd.7th days after surgery in UUO groups than that in Sham group（P^0.01）. The expression in UUO group at 7th day was higher than 3rd day after surgery（P^0.01）. The fi- brosis score,positive TGF-β1, Smad3, Col-I . a-SMA area in UUO group were significantly higher than those of Sham group at 3rd.7th days （P〈0.01） ,Which at 7th day were higher than 3rd day in UUO group（P〈0.01）. The expressions of miRNA-21 in kidney tissue was positive correlations with the fibrosis score（r=0. 888,P%0.01）. The expressions of miRNA-21 in kidney tissue was positive correlations with TGF-131 ,Smad3,Col- T ,a-SMA（r=0. 799,0. 849,0. 882,0. 896 ,P〈0.01）. Conclusion The expres- sion of miRNA-21 was upregulated in UUO kidney tissue after model establishment. The RIF degree might be positive correlations with miRNA-21 expression,and TGF-β1/Smad3 signaling pathway positively regulate miRNA-21 to mediate rats RIF.

关 键 词：微RNAS 输尿管 梗死 转化生长因子β Smad3蛋白质 

分 类 号：R692[医药卫生—泌尿科学]