微小RNA-206对apoE^(-/-)动脉粥样硬化小鼠肝脏X受体α表达的影响

Effect of miRNA-206 on expression of liver X receptor α in apoE^(-/-) mice with atherosclerosis

目的探讨微小RNA(mi R)-206对apo E-/-动脉粥样硬化小鼠肝脏X受体α(LXRα)表达的影响。方法取4周龄apo E-/-小鼠30只,喂以高脂饮食,14周后随机分成对照组、mi R-206 mimic组、mi R-206 inhibitor组,每组10只。尾静脉采血检测总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),油红O染色观察主动脉粥样硬化程度,荧光定量聚合酶链反应(RT-PCR)测定LXRαm RNA表达量,蛋白印迹法测定LXRα蛋白表达量。结果 mi R-206 mimic组HDL-C较对照组升高;mi R-206 inhibitor组与对照组、mi R-206 mimic组相比,TC、LDL均显著升高,HDL明显下降。各组TG无明显不同。苏木精-伊红(HE)染色示对照组主动脉粥样硬化程度较轻,mi R-206 inhibitor组主动脉粥样硬化程度最重,mi R-206 mimic组主动脉粥样硬化病变极其微弱。mi R-206 mimic组肝LXRα表达增多,而mi R-206 inhibitor组表达减少。结论mi R-206可能与LXRα构成反馈环,共同调节胆固醇逆转运。

Objective To investigate the effect of miR-206 on the expression of liver X receptor α （LXRα） in apoE-/-mice with atherosclerosis. Methods Thirty apoE-/-mice aged 4 weeks old were included in the study, and fed with Western diet. All mice were randomly divided into the control group, miR-206 mimic group and miR-206 inhibitor group after 14 weeks （n=10 each）. Blood samples at caudal veins were collected to measure the levels of total cholesterol （TC）, triglyceride （TG）, high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C）. The severity of aortic atherosclerosis was determined by red oil O staining. Levels of LXRαmRNA and protein were determined by RT-PCR and Western blot, respectively. Results The HDL-C level increased in miR-206 mimic group compared with that in control group. Compared with the control group and miR-206 mimic group, significantly increased TC and LDL-C levels and decreased HDL-C level were found in miR-206 inhibitor group. There was no significant difference in TG among different groups. Red O staining showed mild aortic atherosclerosis in control group, most severe disease in the miR-206 inhibitor group, and very modest lesion of aortic atherosclerosis in the miR-206 mimic group, respectively. The LXRαexpression increased in miR-206 mimic group and decreased in miR-206 inhibitor group. Conclusion miR-206 may interact with LXRα in forming a feedback loop to regulate the reverse cholesterol transport.