miR-29b抑制剂降低小鼠肝脏内胆固醇合成

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (12): 1719-1723.

miR-29b抑制剂降低小鼠肝脏内胆固醇合成

蔡君艳^*

东南大学附属中大医院心血管内科, 江苏南京 210000

收稿日期:2020-08-23 修回日期:2021-05-06 发布日期:2021-12-03
通讯作者: *caijunyanzi@126.com
基金资助:
国家自然科学基金(81600677)

miR-29b inhibitor reduces cholesterol synthesis of liver in mice

CAI Jun-yan^*

Department of Cardiology, Zhongda Hospital Affiliated to Southeast University, Nanjing 210000, China

Received:2020-08-23 Revised:2021-05-06 Published:2021-12-03
Contact: *caijunyanzi@126.com

摘要/Abstract

摘要： 目的探究miR-29b对高胆固醇血症小鼠肝脏中胆固醇合成的影响及其可能的机制。方法将C57/BL6小鼠随机分为正常饮食组(Con组)、高脂饮食组(HF组)、正常饮食+miR-29b抑制剂对照组(Con+shRNA组)、正常饮食+miR-29b抑制剂组(Con+antago组)、高脂饮食+miR-29b抑制剂对照组(HF+shRNA组)、高脂饮食+miR-29b抑制剂组(HF+antago组)。8周后测定血浆、肝脏中总胆固醇。RT-qPCR检测miR-29b、沉默调节蛋白1(sirtuin-1,SIRT1)的mRNA表达。Western blot检测肝脏中胆固醇合成相关蛋白的表达。结果 1)与正常饮食组相比,高脂饮食组血浆和肝脏中miR-29b表达升高(P＜0.01)。2)与HF+shRNA组相比,HF+antago组血浆和肝脏中总胆固醇降低,肝脏中SIRT1表达增加(P＜0.01),固醇反应元件结合蛋白(sterol response element binding protein 2, SREBP2) (P＜0.01)和羟甲基戊二酸单酰CoA还原酶(3-hydroxy-3methylglutaryl CoA reductase, HMGCR) 表达减少(P＜0.01)。结论高胆固醇血症小鼠血浆和肝脏中miR-29b表达增加,miR-29b抑制剂可减少肝脏内胆固醇合成。

关键词: miR-29b, 胆固醇合成, 沉默调节蛋白1

Abstract: Objective To investigate the effects and mechanism of miR-29b on the cholesterol synthesis in the liver of hypercholesterolemia mice. Methods C57/BL6 mice were divided into 6 groups: 10 in control group was fed with normal diet, 10 in HF group was fed with Paigen diet, 6 in Con+shRNA group, 6 in Con+antago group, 6 in HF+shRNA group and 6 in HF+antago group. The Con+shRNA group and HF+shRNA group were injected with scrambled shRNA (2.5 mg/kg); Con+antago group and HF+antago group were injected with miR-29b antagomir (2.5 mg/kg). Total cholesterol in the plasma and liver was measured after 8 weeks. RT-qPCR was used to detect expression of miR-29b and SIRT1. Western blot was used to detect the expression of proteins relating cholesterol synthesis in the liver. Results 1) Compared with the control group, the HF group showed increased expression of miR-29b in the plasma and liver. 2) Compared with the HF+shRNA group, the total cholesterol in the plasma and liver of the HF+antago group decreased. miR-29b antagomir increased SIRT1 mRNA and protein expression in the liver. Along with elevated SIRT1 expression, SREBP2 mRNA and protein expression were decreased. Consistently, the expression of HMGCR was reduced by miR-29b antagomir. Conclusions The expres- sion of miR-29b is increased in liver tissue of hypercholesterolemia mice and miR-29b inhibitor can reduce cholesterol synthesis in the liver.

Key words: miR-29b, cholesterol synthesis, SIRT1

中图分类号:

R339.6

蔡君艳. miR-29b抑制剂降低小鼠肝脏内胆固醇合成[J]. 基础医学与临床, 2021, 41(12): 1719-1723.

CAI Jun-yan. miR-29b inhibitor reduces cholesterol synthesis of liver in mice[J]. Basic & Clinical Medicine, 2021, 41(12): 1719-1723.

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