miR-29b抑制剂降低小鼠肝脏内胆固醇合成  

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

作　　者：蔡君艳 CAI Jun-yan(Department of Cardiology, Zhongda Hospital Affiliated to Southeast University, Nanjing 210000, China)

机构地区：[1]东南大学附属中大医院心血管内科,江苏南京210000

出　　处：《基础医学与临床》2021年第12期1719-1723,共5页Basic and Clinical Medicine

基　　金：国家自然科学基金(81600677)。

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。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.

关 键 词：miR-29b 胆固醇合成 沉默调节蛋白1 

分 类 号：R339.6[医药卫生—人体生理学]