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作 者:吴德光[1] 李清贤[2] 王彦富[2] 刘坤[3] 石胜伟[2] 李莎[1]
机构地区:[1]天津医科大学研究生院,天津300070 [2]山东省心脏疾病诊疗重点实验室济宁医学院附属医院心内科 [3]华中科技大学协和医院心血管病研究所
出 处:《临床心血管病杂志》2012年第2期147-152,共6页Journal of Clinical Cardiology
摘 要:目的:通过研究黄芪多糖(APS)对肿瘤坏死因子α(TNF-α)诱导的人急性单核白血病细胞(THP-1)源性泡沫细胞胆固醇流出率、细胞内总胆固醇含量以及细胞膜上脂质流出通道ATP-结合盒转运子A1(ABCA1)表达水平的影响,探讨APS在动脉粥样硬化发展过程中的保护作用。方法:将培养的THP-1源性巨噬细胞分为4组:对照组、单纯TNF-α组、TNF-α+APS组和单纯APS组。分别用RT-PCR法、Western blotting法检测ABCA1的mRNA及蛋白表达水平,闪烁计数法计算胆固醇流出率,酶化学法检测细胞内脂质含量,酶联免疫吸附法(ELISA法)测核因子-κB(NF-κB)的水平。结果:单纯TNF-α组ABCA1的mRNA和蛋白表达量、胆固醇流出率显著低于对照组(P<0.01),细胞内总胆固醇含量、NF-κB的水平显著高于对照组(P<0.05),而单纯APS组与对照组在上述指标上差异无统计学意义(P>0.05);与单纯TNF-α组比较,TNF-α+APS组ABCA1的mRNA和蛋白表达量、胆固醇流出率显著升高(P<0.01),细胞内总胆固醇含量、NF-κB的水平显著降低(P<0.01)。结论:APS能够使泡沫细胞ABCA1的表达及胆固醇流出率上升,而细胞内总胆固醇含量显著下降,并能够减弱泡沫细胞中NF-κB的活化水平。这些发现提示APS能够拮抗TNF-α对于ABCA1的下调作用,从而发挥抗动脉粥样硬化作用。Objective:To explore the effects of astragalus polysaccharide(APS) on cellular cholesterol effluent rate,total cholesterol content,and the expression of ATP-binding cassette transporter A1(ABCA1) of THP-1 from foam cells exposed to TNF-α,and to investigate the protection of APS in atherosclerosis. Method:The THP-1 derived foam cells were divided into four groups: control group,TNF-α group,TNF-α plus APS group,and APS group.The mRNA and protein expression were detected by RT-PCR and Western-blotting,respectively.Cellular cholesterol effluent rate was detected by scintillation counting technique.Total cholesterol content was measured by zymochemistry,and the activity of nuclear factor-kappa B(NF-κB) levels were assayed by ELISA. Result:Compared with the control group,the ABCA1 expression in TNF-α group(including the mRNA and protein) and the cholesterol effluent rate were decreased significantly,and total cholesterol content and NF-κB levels were increased significantly in TNF-α group and TNF-α plus APS group.Compared with TNF-α group,the cholesterol effluent rate increased,total cholesterol content and NF-κB level decreased significantly in TNF-α plus APS group. Conclusion:TNF-α can down-regulate the expression of ABCA1,which plays a vital role in reverse cholesterol transport and determines the process of atherosclerosis.It could enhance the activity of NF-κB in the foam cells.This effect could be attenuated by APS.These findings suggest that APS could protect ABCA1 against the lesion of TNF-α in THP-1 derived foam cells,which may contribute to its anti-atherosclerotic properties.
关 键 词:动脉粥样硬化 黄芪多糖 肿瘤坏死因子Α ATP-结合盒转运子A1 核因子-ΚB
分 类 号:R543.1[医药卫生—心血管疾病]
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