三磷酸腺苷结合盒转运体A1对糖尿病地鼠巨噬细胞内胆固醇外流的影响

目的探讨糖尿病地鼠巨噬细胞内胆固醇外流的改变,尤其是三磷酸腺苷结合盒转运体A1(ABCA1)的功能变化以及与载脂蛋白AI(apoA-I)的相互作用。方法用金黄地鼠高脂及糖尿病模型,分离纯化腹腔巨噬细胞,用外源性apoA-I及8-br-cAMP在体外干预巨噬细胞,测定干预前后巨噬细胞ABCA1表达和细胞内胆固醇含量的变化。结果细胞内胆固醇含量在糖尿病组高于高脂组和正常对照组。apoA-I和8-br-cAMP在体外均增加糖尿病组巨噬细胞ABCA1 mRNA的表达。apoA-I使各组细胞内胆固醇外流均增加,且与孵育时间成正比,胆固醇外流量糖尿病组高于高脂组和正常对照组。结论糖尿病鼠巨噬细胞内胆固醇大量沉积,可能与内源性apoA-I量和功能的改变所引起的ABCA1介导的细胞内胆固醇外流受阻有关。

Effect of ATP-binding cassette transporter A1 on cholesterol efflux from cells

Objective To investigate the potential change of cellular cholesterol efflux and the functional changes of ABCA1 on macrophages from diabetes animals. Methods High energy diet was given to golden hamster to make animal model of hyperlipidemia. Diabetes was induced by a single intraperitoneal injection of STZ (30 mg/kg). Macrophages were isolated and incubated with apoA-I or 8-br-cAMP in vitro. Cellular cholesterol content was measureal before and after treatment by HPLC. Results Intracellular cholesterol content of diabetic animals was higher than that in high energy diet and normal controls. Expression of ABCA1 mRNA was upregulated in diabetic group after incubation with apoA-I and cAMP. When macrophages were incubated with apoA-I, cholesterol efflux increased with the prolongation of incubation time.The amount of intracellular cholesterol efflux in 3 groups of animals showed the following relationship: diabetic animals exceed high energy diet fed animals, and the latter exceeds normal animals. Conclusion Intracellular lipid efflux depends mainly on the presence of extracellular apoA1 as well as membrane ABCA1 protein. The deposition of cholesterol in the macrophage of diabetic and insulin resistant animals may be related to the characteristic changes of quantity and function of apoA1 in these animals.