基础医学与临床 ›› 2009, Vol. 29 ›› Issue (12): 1314-1319.

• 研究论文 • 上一篇    下一篇

2型糖尿病患者单核巨噬细胞胆固醇外流功能的降低与ABCG1表达下调相关

王会娟 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:2009-08-31 修回日期:2009-09-21 出版日期:2009-12-20 发布日期:2009-12-20
  • 通讯作者: 严晓伟

Impaired cholesterol efflux in macrophages of patients with type 2 diabetes mellitus is associated with the decreased expression of ABCG1

Hui-juan WANG, 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
  • Received:2009-08-31 Revised:2009-09-21 Online:2009-12-20 Published:2009-12-20
  • Contact: Xiao-wei YAN

摘要: 目的 研究2型糖尿病患者巨噬细胞内胆固醇外流的变化及ABCA1、ABCG1和SR-B1的表达情况。方法 选取2型糖尿病患者30例(包括合并冠心病组与单纯糖尿病组各15例)和正常对照组15例。分离外周血单核细胞进行巨噬化培养,应用Real-time PCR与Western blot方法测定细胞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及蛋白表达。以5%自身血清及标准血清为接受体测定巨噬细胞胆固醇流出率。 结果ABCG1在2型糖尿病患者巨噬细胞的mRNA与蛋白表达显著低于对照组,而ABCA1与SR-B1的表达在各组间无差异。2型糖尿病患者巨噬细胞的胆固醇流出率也显著低于对照组(P<0.01);ABCG1的mRNA表达与巨噬细胞胆固醇外流率呈显著正相关(r=0.552,r=0.630,P<0.01)。结论 2型糖尿病患者巨噬细胞的胆固醇外流功能明显降低,与ABCG1表达下调相关。

关键词: 胆固醇外流, ABCG1, ABCA1, SR-B1, 糖尿病

Abstract: Objective In the present study, we examined the cholesterol efflux and the expressions of ATP-binding cassette receptor A1 (ABCA1), ABCG1 and scavenger receptor B1 (SR-B1) in monocytes derived macrophages of patients with type 2 diabetes mellitus. Methods and Results Blood was collected from subjects with and without Type 2 diabetes mellitus. Peripheral blood monocytes were differentiated for 72 hours into macrophages, and cholesterol efflux assays, Real-time quantitative PCR and western blot were performed. Macrophages from patients with type 2 diabetes mellitus had a reduction in cholesterol efflux relative to healthy controls. The mRNA and protein expressions of ABCG1 in macrophages from patients with type 2 diabetes mellitus were significantly reduced compared with control subjects. In contrast, the expression of ABCA1 and SR-B1 were similar in both control subjects and diabetic patients. In addition, cellular cholesterol efflux from macrophages to autologous serum and pool serum was significantly correlated with the expression of ABCG1. Conclusion ABCG1 expression and cholesterol efflux are reduced in patients with type 2 diabetes mellitus. This impaired cholesterol efflux significantly correlates with decreased expression of ABCG1.

Key words: cholesterol efflux, ABCA1, ABCG1, SR-B1, diabetes mellitus