固醇调节元件结合蛋白-1对血管紧张素Ⅱ介导的肾小球纤维化的影响  

The Effect of Sterol Regulatory Element-binding Protein-1 on Angiotensin Ⅱ-induced Glomerular Fibrosis

作　　者：李海剑[1] 程根阳[1] 刘栋[1] 肖静[1] 陶雅非[2] 刘慧[3] 赵占正[1] LI Hai-jian;CHENG Gen-yang;LIU Dong;XIAO ring;TAO Ya-fei;LIU Hui;ZHAO Zhan-zheng(Depart- ment of Nephrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, Chin)

机构地区：[1]郑州大学第一附属医院肾内科,河南郑州450052 [2]南阳市中心医院肾病风湿科,河南南阳473009 [3]南阳市中心医院特需一科,河南南阳473009

出　　处：《广东医学》2017年第21期3239-3242,共4页Guangdong Medical Journal

基　　金：河南省科技攻关计划项目(编号:152102310056)

摘　　要：目的探讨固醇调节元件结合蛋白-1(SREBP-1)在血管紧张素Ⅱ(Ang-Ⅱ)诱导肾小球纤维化过程中的作用。方法体外培养人肾小球系膜细胞株HMC,取第三代培养细胞用作实验研究,探讨Ang-Ⅱ对SREBP-1表达刺激的最佳浓度及作用时间。随后采用该时间点和剂量的AngⅡ,将细胞分组为:正常对照组、Ang-Ⅱ组、Ang-Ⅱ+fatostatin组、Ang-Ⅱ+氯沙坦组。逆转录-聚合酶链反应(RT-PCR)检测结缔组织生长因子(CTGF)、Ⅲ型胶原(COLⅢ)、纤维连接蛋白(FN)、SREBP-1和转化生长因子-β_1(TGF-β_1)的mRNA相对表达量。蛋白质免疫印迹法(Western blot)检测CTGF、COLⅢ、TGF-β_1、FN和SREBP-1的蛋白表达量。结果Ang-Ⅱ对SREBP-1表达刺激的最佳浓度及作用时间为100 nmol/L和3 h。与正常对照组相比,Ang-Ⅱ组能够促进HMC中CTGF、COLⅢ、FN的表达,差异有统计学意义(P<0.05)。与Ang-Ⅱ组相比,Ang-Ⅱ+fatostatin组、Ang-Ⅱ+氯沙坦组中CTGF、COLⅢ、TGF-β_1、FN和SREBP-1均明显减少,差异有统计学意义(P<0.05)。结论 Ang-Ⅱ通过血管紧张素1型受体(AT1)激活SREBP/SREBP裂解激活蛋白(SCAP)信号途径,引起TGF-β_1表达增加,进而导致肾小球纤维化。Objective To investigate the role of sterol regulatory element - binding protein - 1 （ SREBP - 1 ） in angiotensin Ⅱ （Ang- Ⅱ ） - induced glomerular fibrosis. Methods HMC cells at Passage 3 were applied. The time course and dose course of Ang Ⅱ - induced SREBP - 1 activation were defined. The HMC Cells were divided into 4 groups, control group, group of Ang - Ⅱ , group of Ang - Ⅱ ＋ losartan, and group of Ang - Ⅱ ＋ fatostatin. RT - PCR and Western blot were used to assess the expression of CTGF, Collagen Ⅲ, TGF - β1 , Fibronectin and SREBP - 1. Re- suits The data showed that Ang - Ⅱ activated SREBP - 1 in the best concentration of 100nmol/L, and action time of 3 hours. Compared to the control group, the expression of CTGF, COL Ⅲ and FN were significantly increased in group of Ang - Ⅱ（ P 〈 0. 05 ）. Compared to the group of Ang - Ⅱ , the expression of CTGF, COL m, TGF - β1 , FN and SREBP - 1 was significantly inhibited in the groups of Ang - Ⅱ ＋ losartan and Ang - Ⅱ ＋ fatostatin （ P 〈 0. 05 ）. Conclusion Ang - Ⅱ activates SCAP/SREBP pathway via AT1 receptor and enhances TGF - β1 induced renal fibrosis.

关 键 词：血管紧张素Ⅱ 固醇调节元件结合蛋白-1 转化生长因子-Β1 肾小球纤维化 

分 类 号：R-332[医药卫生]