同型半胱氨酸对泡沫细胞中LXRα-ABCA1信号通路的影响  

Influence of homocysteine on LXRα-ABCA1 pathway of foam cells

作　　者：王义勇[1] 麻芳[2] 黄晖[1] 沙勇[1] 何琳[1] 金萍[1] 崔莹[1] 贾绍斌[1] 

机构地区：[1]宁夏医科大学总医院心脏中心,银川750004 [2]宁夏医科大学总医院手术室

出　　处：《临床心血管病杂志》2016年第7期726-730,共5页Journal of Clinical Cardiology

基　　金：宁夏医科大学青年基金(No:XQ21327)

摘　　要：目的:探讨同型半胱氨酸(Hcy)通过影响脂代谢调控基因LXRα及其下游靶基因ABCA1和ABCG1的表达致人类急性单核细胞白血病细胞株(THP-1)源性巨噬细胞泡沫化在脂代谢紊乱中的作用。方法:培养THP-1单核细胞,佛波酯、氧化低密度脂蛋白(ox-LDL)共同诱导,采用中性红对巨噬细胞染色,并应用流式细胞技术检测巨噬细胞表面CD14的表达,测定巨噬细胞的含量。分为5组,分别加入0、10、50、100、200μmol/L的Hcy培养24h;采用RT-PCR法检测LXRα、ABCA1、ABCG1的mRNA表达;采用Western Blot法检测LXRα、ABCA1、ABCG1的蛋白表达。结果:实验组(Hcy 10、50、100、200μmol/L)泡沫细胞计数阳性百分率均较对照组升高(均P<0.05),其中以Hcy 100μmol/L组升高明显。在Hcy诱导浓度50μmol/L时巨噬细胞51.26%,CD14表达阳性率53.36%;诱导浓度100μmol/L时巨噬细胞98.5%,CD14表达阳性率73.37%。在不同浓度Hcy干预下,泡沫细胞内LXRα、ABCA1、ABCG1的mRNA及蛋白表达均低于对照组(均P<0.05)。结论:Hcy可降低THP-1源性泡沫细胞内LXRα、ABCA1、ABCG1mRNA及蛋白水平的表达,LXRα可能是Hcy影响脂代谢LXRα-ABCA1信号通路中的靶基因。Objective：To investigate the influence of homocysteine（Hcy）in the disorder of lipid metabolism of THP-1-derived foam cells via affecting the expressions of liver X receptorα（LXRα）and its target gene-ATP-binding cassette subfamily A member 1（ABCA1）and ATP-binding cassette subfamily G member 1（ABCG1）.Method：The THP-1cells were cultured and incubated with phorbool-1-myristate-13-acetate（PMA）and oxidized low density lipoprotein（ox-LDL）to become foam cells.Macrohpages were stained by neutral red and detected the CD14 by flow cytometry.The cells were divided into five groups：0μmol/L Hcy（control group）and 10,50,100,200μmol/L Hcy for 24 hours.RT-PCR was performed to analyze the mRNA expressions of LXRα,ABCA1 and ABCG1.Western blot was performed to analyze the protein expressions of LXRα,ABCA1 and ABCG1.Result：Compared with the control group,the experimental groups（Hcy 10,50,100,200μmol/L）had higher percentage of foam cells（all P0.05）,and the Hcy 100μmol/L group increased most obviously.The CD14 positive rate of Hcy 50μmol/L group was 51.26 %,while the Hcy 100μmol/L was 98.5%.The mRNA as well as protein expressions in all the Hcy groups were lower than those in the control group（all P0.05）.Conclusion：Hcy can reduce the mRNA and protein expressions of LXRα,ABCA1 and ABCG1in THP-1derived foam cells.And LXRαmight be the key target gene in the LXRα-ABCA1 pathway which Hcy induced lipid metabolism.

关 键 词：同型半胱氨酸 巨噬细胞 泡沫细胞 胆固醇逆向转运 肝核受体α ATP结合盒转运子A1 ATP结合盒转运子G1 

分 类 号：R543.5[医药卫生—心血管疾病]