miRNA-34b抑制剂通过调控TIA-1-SG通路缓解肾脏纤维化的机制探讨  

Mechanism of miRNA-34b Inhibitor Alleviating Renal Fibrosis by Regulating TIA-1-SG Pathway

作　　者：华红艳 李建听 夏剑民 Hua Hong-yan;Li Jian-ting;Xia Jian-min(Department of Nephrology,He Xian Memorial Hospital of Panyu District,Guangzhou 511400,Guangdong Province,China)

机构地区：[1]广州市番禺区何贤纪念医院肾病科,广东广州511400

出　　处：《中国社区医师》2022年第21期3-5,共3页Chinese Community Doctors

基　　金：番禺区科技计划项目(2020-Z04-041)

摘　　要：目的:分析miRNA-34b抑制剂通过调控细胞毒颗粒关联RNA结合蛋白1应激颗粒(TIA-1-SG)通路缓解肾脏纤维化的机制。方法:给予CD1小鼠250 mg/kg叶酸诱导肾间质纤维化,给予其miRNA-34b抑制剂(以下简称“抑制剂”)皮下注射,持续4周,注射2次/周。体外细胞实验,对人肾小管上皮细胞(HK2)分别进行miRNA-34b的过表达处理与沉默处理,均使用巨噬细胞上清液进行培养。对比小鼠在注射抑制剂前后的纤维化指标,对比HK2细胞miRNA-34b过表达处理与沉默处理的纤维化相关指标、肾小管损伤指标、miRNA-34b与TIA-1-SG。结果:与小鼠注射miRNA-34b抑制剂前的情况比较,注射后的纤维化指标TGFβ1、纤维连接蛋白与Ⅳ型胶原蛋白均降低,差异具有统计学意义(P<0.05);过表达处理下HK2细胞的肾小管损伤指标、纤维化相关指标与miRNA-34b表达率高于沉默处理下的HK2细胞,过表达处理下HK2细胞的TIA-1-SG表达率低于沉默处理下的HK2细胞,差异具有统计学意义(P<0.05)。结论:TIA-1-SG对缓解肾脏纤维化具有重要作用,miRNA-34b抑制剂能够抑制miRNA-34b表达,进而对其下调TIA-1-SG的过程产生抑制作用,促进TIA-1-SG的表达,进而降低肾损伤指标、炎性指标及纤维化指标。Objective:To analyze the mechanism by which miRNA-34b inhibitor alleviates renal fibrosis by regulating the cytotoxic granule-associated RNA binding protein 1 stress granule(TIA-1-SG)pathway.Methods:CD1 mice were given 250 mg/kg folic acid to induce renal interstitial fibrosis,and then given miRNA-34b inhibitor(hereinafter referred to as"inhibitor")subcutaneously for 4 weeks,twice a week.In vitro cell experiment:human renal tubular epithelial cells(HK2)were subjected to miRNA-34b overexpression and silencing,and both were cultured with the supernatant of macrophages.The fibrosis indicators of mice before and after the inhibitor injection were compared.After HK2 cells were subjected to miRNA-34b overexpression and silencing,the fibrosis-related indicators,renal tubular damage indicator,miRNA-34b and TIA-1-SG were compared.Results:Compared with the mice before injection of miRNA-34b inhibitor,the fibrosis indicators TGFβ1,fibronectin and type IV collagen were decreased after injection,and the difference was statistically significant(P<0.05).Compared with HK2 cells under silencing treatment,HK2 cells under overexpression treatment had higher expression rates of renal tubular damage,fibrosis-related indicators and miRNA-34b,and lower TIA-1-SG expression rates,and the difference was statistically significant(P<0.05).Conclusion:TIA-1-SG plays an important role in alleviating renal fibrosis.miRNA-34b inhibitors can inhibit the expression of miRNA-34b,which inhibits the process of down-regulating TIA-1-SG and promotes the expression of TIA-1-SG,thus reducing kidney injury indicator,inflammatory indicators and fibrosis indicators.

关 键 词：miRNA-34b 抑制剂 TIA-1-SG 肾脏纤维化 

分 类 号：R692[医药卫生—泌尿科学]