miR-98通过调控ox-LDL诱导血管内皮损伤抑制动脉粥样硬化形成的作用机制研究

Inhibition of atherosclerosis formulation by miR-98 through regulating ox-LDL to induce vascular endothelial injury: a study on effective mechanism

目的探讨miR-98对动脉粥样硬化(AS)发生、发展的调控作用及可能的作用机制。方法比较AS患者和健康受试者血浆微小核糖核酸(miR-98)和凝集素样氧化低密度脂蛋白受体-1(LOX-1)表达情况,采用MTT法检测氧化低密度脂蛋白(ox-LDL)干预对人主动脉内皮细胞(HAEC)、人主动脉平滑肌细胞(HASMC)和小鼠腹腔巨噬细胞增殖活性的影响,采用RT-PCR法检测ox-LDL干预对miR-98表达的影响,采用RT-PCR和Western blot法检测miR-98模拟物或抑制物转染细胞对LOX-1、细胞核因子κB(NF-κB p65)和内皮素-1(ET-1)表达的影响。结果与健康受试者比较,AS患者血浆miR-98表达下调,LOX-1表达上调(P<0.05)。在ox-LDL 15 ug/ml干预后,HAEC细胞和巨噬细胞增殖活性最强(P<0.05),HAEC和巨噬细胞中miR-98表达量较AS组明显降低(P<0.05)。与对照组和miR-98抑制物转染细胞比较,miR-98过表达可明显抑制LOX-1、NF-κB p65和ET-1的表达量(P<0.05)。结论 miR-98可能通过负性调控NF-κB信号通路抑制ox-LDL诱导的动脉粥样硬化早期血管内皮损伤过程。

Objective To investigate the regulation effect of miR-98 on occurrence and development of atherosclerosis(AS)and possible effective mechanism.Methods The expressions of plasma miR-98 and lectinlike oxidized low-density lipoprotein receptor-1(LOX-1)were compared between AS patients(AS group)and healthy controls(control group).The influence of oxidized low density lipoprotein(ox-LDL)on proliferative activities of HAEC,HASMC and macrophage was detected by using MTT.The influence of ox-LDL intervention on expression of miR-98 was detected by using RT-PCR.The influence of miR-98 simulant transfection cells or inhibitor transfection cells on expressions of LOX-1,nuclear factor-κB(NF-κB)and endothelin-1(ET-1)in were detected by using RT-PCR and Western blotting assay.Results The expression of miR-98 decreased and LOX-1 expression increased in AS group compared with control group(P<0.05).After ox-LDL(15 ug/mL)intervention,proliferative activities of HAEC and macrophage were the highest(P<0.05),and expression of miR-98 in HAEC and macrophage decreased significantly compared with AS group(P<0.05).The over-expression of miR-98 imulant transfection cells inhibited significantly expressions of LOX-1,NF-κB p65 and ET-1 compared with miR-98 inhibitor transfection cells(P<0.05).Conclusion MiR-98 can relieve vascular endothelial injury induced by negatively regulating NF-κB signal pathway to inhibit ox-LDL in early AS stage.