基础医学与临床 ›› 2009, Vol. 29 ›› Issue (5): 510-514.

• 研究论文 • 上一篇    下一篇

2型糖尿病患者的高密度脂蛋白和乏脂血清对细胞内胆固醇外流的影响

王会娟 孟晓梅 陈连凤 方全 严晓伟   

  1. 中国医学科学院 北京协和医学院 北京协和医院 心内科 中国医学科学院 北京协和医学院 北京协和医院 心内科 中国医学科学院 北京协和医学院 北京协和医院 心内科 中国医学科学院 北京协和医学院 北京协和医院 心内科
  • 收稿日期:2009-01-13 修回日期:2009-02-12 出版日期:2009-05-25 发布日期:2009-05-25
  • 通讯作者: 严晓伟

Effects of high-density lipoprotein and lipoprotein-deficient serum on intracellular cholesterol efflux in patients with type 2 diabetes mellitus

Hui-juan WANG, Xiao-mei MENG, Lian-feng CHEN, Quan FANG, Xiao-wei YAN   

  1. Dept. of Cardiology, PUMC Hospital, CAMS&PUMC Dept. of Cardiology, PUMC Hospital, CAMS&PUMC Dept. of Cardiology, PUMC Hospital, CAMS&PUMC Dept. of Cardiology, PUMC Hospital, CAMS&PUMC
  • Received:2009-01-13 Revised:2009-02-12 Online:2009-05-25 Published:2009-05-25
  • Contact: Xiao-wei YAN

摘要: 目的 研究2型糖尿病患者高密度脂蛋白(HDL)及乏脂血清(LPDS)介导的细胞内胆固醇外流变化。方法 选取2型糖尿病患者13例和正常对照组17例,分离HDL和LPDS。利用人皮肤纤维母细胞(HSF)和人肝癌细胞(HepG2细胞)为实验细胞系,测定ATP结合盒受体A1(ABCA1)、ATP结合盒受体G1(ABCG1)和清道夫受体B1(SR-B1)的mRNA和蛋白表达。以HDL、LPDS为接受体测定3H胆固醇在上述细胞的胆固醇流出率。 结果HepG2 细胞高表达SR-B1;HSF经22-羟基胆固醇刺激后高表达ABCA1。2型糖尿病患者的HDL诱导HepG2细胞的胆固醇流出率显著低于对照组(P<0.001);而LPDS介导的HSF细胞的胆固醇外流率在两组间无显著差异。 结论 2型糖尿病患者的HDL诱导HepG2细胞的胆固醇外流功能明显降低,提示HDL功能异常在糖尿病患者的细胞内胆固醇积聚及动脉粥样硬化发展过程中发挥重要作用。

关键词: 高密度脂蛋白, 无脂血清, 糖尿病, 胆固醇外流

Abstract: Objective In the present study, we examined the effects of high-density lipoprotein (HDL) and lipoprotein-deficient serum (LPDS) isolated from patients with type 2 diabetes mellitus on cholesterol efflux through human skin fibroblast (HSF) and human hepatoma cell line (HepG2). Methods and Results Blood was collected from 13 patients with type 2 diabetes mellitus and 17 healthy volunteers and HDL and LPDS were isolated. Cholesterol efflux assays, RT-PCR and western blot were performed on HSF and HepG2 cells. The HepG2 cells have a high expression of scavenger receptor B1(SR-B1) and lack functional ATP-binding cassette receptor A1(ABCA1) and ATP-binding cassette receptor G1(ABCG1) while HSF cells express SR-B1 at very low levels and have a high expression of ABCA1 pretreated with 22-OH cholesterol. The cholesterol efflux from HepG2 cells to HDL isolated from patients with diabetes decreased significantly compared to controls. However, cholesterol efflux from HSF cells to LPDS was not different between groups. Conclusion The function of HDL involving cholesterol efflux in type 2 diabetes mellitus was impaired while cholesterol efflux induced by LPDS from HSF cells was maintained, implying that HDL plays a critical role in mediation of intracellular cholesterol accumulation and progression of atherosclerosis in patients with type 2 diabetes.

Key words: High-density lipoprotein, Lipoprotein-deficient serum, diabetes mellitus, cholesterol efflux