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。
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.
出处
《中国动脉硬化杂志》
CAS
CSCD
北大核心
2014年第9期885-890,共6页
Chinese Journal of Arteriosclerosis
基金
山西省科技攻关资助项目(20100311098-4)
