摘要
目的观察坎地沙坦(CAN)对氧化低密度脂蛋白(ox-LDL)诱导急性单核白血病细胞(THP-1)源性泡沫细胞及对三磷腺苷结合盒转运子A1(ABCA1)表达水平的作用。方法 THP-1源性细胞加入160 nmol.L-1佛波酯,在RPMI-1640液中孵育48 h,将其诱导分化为巨噬细胞后随机分为3组,对照组加入50 mg.L-1ox-LDL培养液孵育48 h;血管紧张肽Ⅱ(AngⅡ)组加入1×10-6mol.L-1AngⅡ后再加入50 mg.L-1ox-LDL培养液孵育48 h;CAN组加入1×10-6mol.L-1CAN后再加入1×10-6mol.L-1AngⅡ孵育,然后以50 mg.L-1ox-LDL处理48 h。分别采用油红O染色观察细胞内脂滴变化,酶化学法测定总胆固醇和胆固醇酯含量,Western blotting法检测ABCA1蛋白表达水平。结果 AngⅡ作用后,细胞内脂滴明显增多,细胞内总胆固醇和胆固醇酯含量及胆固醇酯/总胆固醇比值明显升高,ABCA1蛋白表达水平降低(P<0.05)。CAN能减少泡沫细胞内脂滴形成,导致细胞内总胆固醇和胆固醇酯含量及胆固醇酯/总胆固醇比值明显降低,一定程度上调泡沫细胞转运蛋白ABCA1表达(P<0.05),促进细胞内胆固醇酯流出。结论 AngⅡ减少泡沫细胞中ABCA1的表达,CAN可通过阻断AngⅡ1型受体促进ABCA1的表达及胆固醇酯流出。
Objective To investigate the effect of candesartan （CAN） on the formation of THP-l-derived foam cells and protein ABCA1 expression. Methods THP-l-derived cells were added with phorbol 12-myristate 13-acetate （PMA, 160 nmol·L-1 ） and cultured in RPMI-1640 for 48 h to differentiate into macrophages. The THP-l-derived macrophages were randomly divided into three groups. In the ox-LDL group,macrophage cells were incubated with 50 mg · L-1 ox-LDL medium for 48 h; In the Ang U group, cells were incubated with 1×10-6mol·L-1 Ang II, followed by 50 mg · L-1 ox-LDL for 48 h; In the CAN group, macrophages were incubated with 1×10-6mol·L-1 CAN and 1×10-6mol·L-1 Ang II, followed by 50 mg ·L-1 ox- LDL for 48 h. Lipid droplets in the cytoplasm were observed by Oil Red O staining. The contents of intracellular total cholesterol and cholesteryl esters were measured by enzymology. Western blotting was performed to determine the expression of ABCAI protein. Results In the Ang H group, intracellular red O-positive droplets, the contents of intracellular total cholesterol and cholesteryl ester, and the ratio of cholesteryl ester to total cholesterol were significantly increased （ P〈0.05 ）, and the expression of ABCAI protein was decreased in THP-1-derived macrophages,compared to the ox-LDL group. As compared to the Ang H group, CAN decreased the formation of lipid droplets in foam cells, the contents of intracellular total cholesterol, and the ratio of cholesteryl ester to total cholesterol （ P 〈 0. 05 ）, up-regulated the expression of ABCA1 protein, and promoted intacellular cholesterol ester to outflow. Conclusion Ang H decreases ABCA1 expression in the foam cells, and CAN activates ABCA1 expression and promotes cholcsteryl ester efflux through angiotensin AT1 receptor blockage.
出处
《医药导报》
CAS
北大核心
2013年第8期989-992,共4页
Herald of Medicine
