MicroRNA27a抑制肝星状细胞脂质代谢分子机制的初步研究  

A preliminary study on the molecular mechanism of microRNA-27a inhibiting lipid metabolism of hepatic stellate cells

作　　者：徐梓馨 罗昕 罗声政[1] 徐铭益[1] 林仁坤 XU Zi-xin;LUO Xin;LUO Sheng-zheng;XU Ming-yi;LIN Ren-kun(Department of Gastroenterology,Shanghai General Hospital,Shanghai JiaoTong University School of Medicine,Shanghai 200080,China)

机构地区：[1]上海交通大学附属第一人民医院消化内科,200080

出　　处：《肝脏》2020年第9期994-997,共4页Chinese Hepatology

基　　金：国家自然科学基金(81570547,81770597);国家科技部“十三五”重大专项(2017ZX10203202003005)。

摘　　要：目的初步探究microRNA-27a(miR-27a)在肝星状细胞中脂质代谢的分子机制。方法 C57BL/6实验小鼠随机分组为高脂加CCL4组和普食加CCL4组,HE和天狼星红染色检测小鼠肝组织病理改变情况,PCR检测高脂加CCL4组和普食加CCL4组小鼠肝组织中miR-27a表达水平及FAS、SCD1相关mRNA表达水平。结果与对照组miR-27a的表达量比较,实验组结果表明miR-27a在PA刺激后的LX2细胞中表达下降;对比普食加CCL4组,高脂加CCL4组小鼠肝组织中miR-27a表达下降,差异均具有统计学意义(P<0.05);相比较空白对照组,过表达miR-27a后的LX2细胞脂质沉积明显减轻,FAS、SCD1相关mRNA表达水平显著降低,高脂加CCL4组小鼠促脂质合成因子FAS、SCD1相关mRNA表达上升,差异均具有统计学差异(P<0.05)。结论 miR-27a可能是通过抑制FAS、SCD1的表达抑制肝星状细胞脂质代谢,减轻肝脏脂质沉积,延缓肝脂肪变的发生发展。Objective To investigate the molecular mechanism of microRNA27 a inhibiting the lipid metabolism of hepatic stellate cell.Methods LX2 cells were stimulated by palmitic acid(PA),the expression level of miR-27 a was tested by PCR;After Overexpression of miR-27 a,lipid deposition of LX2 cells was tested by oil red staining.The mRNA expression of FAS and SCD1 was verified by qPCR.C57 BL/6 mice were randomly divided into two group:high-fatty diet with CCL4 group(HFD+CCL4)and low fatty diet with CCL4(LFD+CCL4).The pathological changes of liver tissues in mice were detected by hematoxylin eosin(HE)and Sirius red staining.Besides,qPCR was applied to detect the relative expression of microRNA27 a and the mRNA expression of FAS and SCD1 in different group.Results Comparing with the control group,the expression of miR27 a in LX2 cell in experimental group decreased after stimulated by PA;In the mouse model,the expression of miR27 a in HFD with CCL4 group also decreased,compared with LFD with CCL4(P<0.05).Compared with blank control group,lipid deposition in LX2 cells of overexpressing miR-27 a was significantly reduced as well as the mRNA expression of FAS and SCD1,however,the expression of FAS and SCD1 in HFD with CCL4 group were increased(P<0.05).Conclusion MiR-27 a can inhibit the lipid synthesis of hepatic stellate cells,reduce liver lipid deposition and delay the development of liver fatty change by inhibiting the expression of FAS and SCD1.This provides a new thought for the treatment of nonalchoholic fatty liver disease.

关 键 词：微小RNA 脂肪酸合酶 硬脂酰辅酶A去饱和酶1 非酒精性脂肪性肝病 

分 类 号：R575.5[医药卫生—消化系统]