血管紧张素(1-7)和血管紧张素Ⅱ对THP-1源性泡沫细胞胆固醇外流的影响
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山西省科技攻关资助项目(20100311098-4)


Effects of Ang(1-7) and AngⅡ on the Cholesterol Efflux in THP-1 Derived Foam Cells
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    摘要:

    目的 观察血管紧张素(1-7)[Ang(1-7)]及血管紧张素Ⅱ(AngⅡ)对THP-1源性泡沫细胞B族Ⅰ型清道夫受体(SR-BⅠ)、ATP结合盒转运体A1(ABCA1)表达及胆固醇外流的影响。方法 将THP-1单核细胞加入100 nmol/L佛波酯(PMA) 48 h诱导分化为THP-1源性巨噬细胞,加入氧化型低密度脂蛋白(ox-LDL)建立泡沫细胞模型。随机分为五组:空白对照组、AngⅡ组、Ang(1-7)组、Ang(1-7)+AngⅡ组及AngⅡ+Ang(1-7)+A-779组[A-779为Ang(1-7)受体特异性阻滞剂]。分别运用RT-PCR及Western blot方法检测SR-BⅠmRNA、ABCA1mRNA及其蛋白的表达,用液体闪烁计数仪检测胆固醇流出率的变化。结果 与空白对照组相比,加用AngⅡ组SR-BⅠmRNA、ABCA1mRNA及其蛋白的表达均明显减弱且胆固醇外流减少(P<0.05);与AngⅡ组比较,加用Ang(1-7)促进SR-BⅠmRNA、ABCA1mRNA及其蛋白的表达,胆固醇外流增加(P<0.05);与AngⅡ+Ang(1-7)组比较,AngⅡ+Ang(1-7)+A-779组SR-BⅠmRNA、ABCA1mRNA及其蛋白的表达减弱、胆固醇外流减少(P<0.05),但与AngⅡ组比较差异无统计学意义(P>0.05)。结论 AngⅡ抑制THP-1源性泡沫细胞SR-BⅠ、ABCA1的表达并减少胆固醇外流,而Ang(1-7) 通过其特异性受体MAS受体可减弱AngⅡ的作用,促进胆固醇外流,从而对动脉粥样硬化的进展起到抑制作用。

    Abstract:

    Aim To investigate the effects of angiotensin(1-7)[Ang(1-7)] and angiotensinⅡ(AngⅡ) on scavenger receptor class B type Ⅰ(SR-BⅠ), ATP-binding cassette transporter A1(ABCA1) and cholesterol efflux in THP-1 derived foam cells. Methods Human monocytic cell line (THP-1) were induced into macrophages by 100 nmol/L phorbol myristate acetate(PMA) for 48 h, and treated with oxidized low density lipoprotein (ox-LDL) to construct the foam cells, then were randomly allocated into five groups: control group, AngⅡ group,Ang(1-7) group,Ang(1-7)+AngⅡ group and AngⅡ+Ang(1-7)+A-779 group. The mRNA and protein expression of SR-BⅠ, ABCA1 were determined by RT-PCR and Western blot, the intracellular cholesterol efflux rate was detected by liquid scintillator. Results Compared with the control group, AngⅡ decreased SR-BⅠ and ABCA1 in both protein and mRNA, and inhibited the cholesterol efflux(P<0.05). Those effects could be attenuated by cotreatment with Ang(1-7)(P<0.05). However when incubated with A-799, an inhibitor of Ang(1-7), the effects of Ang(1-7) on promoting the expression of SR-BⅠ, ABCA1 and the cholesterol efflux were significantly abolished(P<0.05). Conclusion In THP-1 derived foam cells, Ang(1-7) via its specific receptor MAS attenuates the reduction of the expression of SR-BⅠ and ABCA1 induced by AngⅡ, and increases the cholesterol efflux.

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柴婵娟,杨慧宇,杨志明,梁 斌,阎 丰,武 瑞,边云飞.血管紧张素(1-7)和血管紧张素Ⅱ对THP-1源性泡沫细胞胆固醇外流的影响[J].中国动脉硬化杂志,2014,22(9):885~890.

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  • 收稿日期:2014-02-21
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