厄贝沙坦对巨噬细胞凝集素样氧化低密度脂蛋白受体(LOX-1)基因及蛋白表达的影响

Effects of irbesartan on expression of lectin-like oxidized low-density lipoprotein receptor-1 mRNA and protein in cultured THP-1 cells

目的研究不同浓度厄贝沙坦对血管紧张素Ⅱ(AngⅡ)诱导的人单核/巨噬细胞系(THP-1)凝集素样氧化低密度脂蛋白受体(LOX-1)mRNA和蛋白表达的影响,并探讨其可能的机制。方法 THP-1细胞经0.16μmoL/L佛波酯诱导分化后,将细胞分为3组:对照组、AngⅡ组、厄贝沙坦干预组,干预组分别加入不同浓度厄贝沙坦孵育2 h后,再加入AngⅡ1×10-6moL/L孵育24 h,用荧光定量PCR和细胞酶联免疫法检测(LOX-1)mRNA和蛋白表达。结果与对照组比较,Ang II可明显上调THP1细胞(LOX-1)mRNA和蛋白表达,差异有统计学意义(P<0.05)。不同浓度厄贝沙坦均能抑制(LOX-1)蛋白表达(P<0.05),并且随着厄贝沙坦浓度降低,抑制作用减低,即两者呈浓度依赖性。结论厄贝沙坦以浓度依赖方式抑制AngⅡ诱导的THP1细胞(LOX-1)mRNA和蛋白表达,减少巨噬细胞通过(LOX-1)途径的氧化低密度脂蛋白(oxLDL)摄入,影响泡沫细胞的发生、发展,发挥其抗动脉粥样硬化(AS)作用。

Objective To investigate the influence of irbesartan on expression of lectin-like oxidized low-density lipoprotein receptor-1 mRNA and protein in cultured THP-1 cells Methods THP-1 cells were differentiated by incubation with 160nM PMA for 72 hours.The cells were divided into three groups：control group, Ang IIgroup and irbesartan intervention group. The intervention groups were first treated with several concentration irbesartan for 2 hours, then coincubated with Ang II 1 × 10^-6moL/L for 24h, Real time PCR and enzyme-linked immunosorbent assay technology were used to detect （LOX-1） mRNA and protein expression.Results Ang II induced the increase of THP-1 （LOX-1） mRNA and protein expression（P〈0.05）. Several concentration irbesartan groups blocked Ang II-induced （LOX-1） mRNA and protein expression,The decrease in （LOX-1） expression was dependent on irbesartan concentration. Conclusion Irbesartan can blocke Ang II -induced（LOX-1） mRNA and protein expression in a concentration-dependent and reduce intake of macrophages on the oxidized low density lipoprotei via （LOX-1） pathway, affecting the foam cell development,exert their effect on anti-atherosclerosis.