动脉粥样硬化患者外周血miR-152表达变化机制及其与血脂水平的相关性

目的 探讨动脉粥样硬化(AS)患者外周血miR-152及其启动子区DNA甲基化水平改变,并分析其与血脂水平的相关性.方法 选择经颈动脉多普勒超声检查确诊为AS患者40例(AS组),并选择同期健康体检者40例作为对照(对照组).生化分析仪检测两组患者血脂水平;实时荧光定量PCR(RT-qPCR)检测两组患者外周血miR-152的表达水平;巢式降落式甲基化特异性PCR(nt-MSP)检测两组患者外周血miR-152 DNA甲基化水平;采用SPSS 19.0统计软件对miR-152的表达水平与血脂水平进行相关性分析.结果 AS组患者血清总胆固醇(TC)、三酰甘油(TG)和低密度脂蛋白(LDL)显著高于对照组(均P<0.01),而高密度脂蛋白(HDL)则显著低于对照组(P<0.01);AS组患者外周血miR-152的表达水平较对照组显著降低(P<0.01),而miR-152启动子区DNA甲基化水平较对照组显著升高(P<0.01);相关性分析结果显示,miR-152的表达水平与TC、TG和LDL水平呈负相关,相关系数分别为-0.71、-0.69和-0.58;与HDL呈正相关,相关系数为0.61.结论 AS患者外周血miR-152启动子区DNA甲基化程度升高使其表达水平降低,可能影响血液中血脂含量并最终导致AS的发生、发展.

The mechanism of miR-152 expression alteration in peripheral blood of patients with atherosclerosis and its cor-relation with blood lipid levels.

Objective To investigate the mechanism of miR -152 expression alteration in peripheral blood of pa-tients with atherosclerosis ( AS) and its correlation with blood lipid levels .Methods Forty cases with AS ( AS group) di-agnosed by carotid Doppler ultrasonography between January 2015 to January 2015 were included in our hospital , and 40 health participants for physical examination (control group) were included at the same period as control .Biochemical ana-lyzer was used to detect the blood lipid levels in both groups .Real-time fluorescent quantitative PCR ( RT-qPCR) was used to detect the expression of miR -152 in peripheral blood .Nest type land type methylation specific PCR ( nt-MSP) was used to detect the DNA methylation levels of miR -152 promoter region .SPSS19.0 statistics software was used to ana-lyze the correlation between miR -152 expression and blood lipid levels .Results The serum total cholesterol ( TC) , tri-glyceride (TG), low density lipoprotein (LDL) of AS patients were significantly higher than control group (P<0.01, P<0.01, P<0.01), with significantly lower high -density lipoprotein (HDL) (P<0.01).The expression of miR-152 of AS group was significantly lower than control group (P<0.01), and the DNA methylation level of miR -152 pro-moter region was significantly higher than control group (P<0.01).The expression level of miR -152 was significantly negatively correlated with TC, TG and LDL levels (OR=0.5018, 0.4280 and 0.5018, respectively); and positively correlated with HDL ( OR=0.3670) .Conclusion The methylation of miR -152 promoter region of DNA induces the down-regulation of its expression , this may affect blood lipid levels and eventually lead to the development of AS .