瑞巴派特通过抑制miR-877-5p的表达减轻阿司匹林对人胃黏膜上皮细胞损伤的研究  

Study on Rebamipide alleviates Aspirin-induced injury through inhibiting the expression of miR-877-5p in human gastric epithelial cells

作　　者：韩维维[1] 谈路轩 李超[1] 何帮顺[2] 樊叶 张振玉[1] HAN Weiwei;TAN Luxuan;LI Chao;HE Bangshun;FAN Ye;ZHANG Zhenyu(Department of Gastroenterology;Central Laboratory,Affiliated Nanjing Hospital of Nanjing Medical University（Nanjing First Hospital）,Nanjing 210006;Department of Emergency,the People＇ s Liberation Army General Hospital of Nanjing,China)

机构地区：[1]南京医科大学附属南京医院(南京市第一医院)消化科 [2]南京医科大学附属南京医院(南京市第一医院)中心实验室 [3]解放军南京总医院急诊科

出　　处：《胃肠病学和肝病学杂志》2018年第6期661-665,共5页Chinese Journal of Gastroenterology and Hepatology

摘　　要：目的研究瑞巴派特是否通过抑制miR-877-5p的表达减轻阿司匹林对人胃黏膜上皮细胞GES-1的损伤。方法体外培养GES-1细胞株,将其分为空白对照组、阿司匹林(IC10浓度)损伤组和阿司匹林(IC10浓度)联合不同浓度瑞巴派特(0.2、0.5、1.0 mmol/L)保护组,利用qRT-PCR检测miR-877-5p的表达情况。转染miR-877-5p inhibitors到阿司匹林损伤组的细胞,转染miR-877-5p mimics到0.5 mmol/L瑞巴派特保护组的细胞,CCK-8法检测细胞增殖情况,流式细胞技术检测细胞凋亡情况。利用miRNA靶基因数据库预测miR-877-5p的靶基因,并利用生物信息学分析miR-877-5p的功能。结果阿司匹林损伤组中的miR-877-5p表达量明显高于瑞巴派特保护组(P<0.05),miR-877-5p表达量在保护组中随着瑞巴派特浓度增加而逐渐降低(F=71.87,P<0.05)。转染miR-877-5p inhibitors能减轻阿司匹林对人胃黏膜上皮细胞增殖的抑制作用(P<0.05),抑制细胞的凋亡(P<0.05)。转染miR-877-5p mimics能抑制瑞巴派特对细胞的增殖效应(P<0.05),促进细胞凋亡(P<0.05)。生物信息学发现,miR-877-5p共有945个靶基因,这些靶基因多参与c AMP信号通路、MAPK信号通路、PI3K-Akt信号通路等发挥作用。结论瑞巴派特通过抑制miR-877-5p的表达,减轻阿司匹林对人胃黏膜上皮细胞GES-1的损伤。Objective To investigate whether Rebamipide plays a protective role on Aspirin-induced injury through inhibiting the expression of miR-877-5p in human gastric epithelial cells（ GES-1）. Methods Cultured GES-1 cells were divided into control group,Aspirin injured group and different concentrations（ 0. 25,0. 5,1. 0 mmol/L） Rebamipide plus Aspirin groups. The expression of miR-877-5p was detected by qRT-PCR. The Aspirin treated cells were transfected with miR-877-5p inhibitors. The combination of Rebamipide and Aspirin treated cells were transfected with miR-8877-5p mimics. Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry. The targeted genes of miR-877-5p were predicted by miRNA target databases,the GO and KEGG pathway were analyzed by DAVID database. Results qRT-PCR showed that the expression of miR-877-5p in Aspirin group was the highest than others. The expressions of miR-877-5p in different concentrations（ 0. 25,0. 5,1. 0 mmol/L） of Rebamipide plus Aspirin groups were 4. 28 ± 0. 25,2. 45 ± 0. 28 and 1. 47 ± 0. 17. The expression of miR-877-5p was gradually decreased with the increase of concentration of Rebamipide. The CCK-8 assay and flow cytometry showed that miR-877-5p mimics transfection blocked proliferations and promoted apoptosis in combination of Rebamipide and Aspirin treated cells,while miR-877-5p inhibitors promoted proliferation and inhibited apoptosis in Aspirin treated cells. The pathways of miR-877-5p targeted genes were almost focused on c AMP signaling pathway,MAPK signaling pathway,PI3K-Akt signaling pathway,and so on. Conclusion Rebamipide alleviates Aspirin-induced injury through inhibiting the expression of miR-877-5p in human gastric epithelial cells.

关 键 词：瑞巴派特 阿司匹林 胃黏膜损伤 miR-877-5p 

分 类 号：R573[医药卫生—消化系统]