辛伐他汀对新诊断2型糖尿病患者单核巨噬细胞胆固醇外流的影响  

Effect of simvastatin on cholesterol efflux from macrophages of patients with newly diagnosed type 2 diabetes mellitus

作　　者：彭扬[1] 霍翠翠[1] 闫芳[1] 吕静[1] 白雪[1] 李慧[1] 

机构地区：[1]中国医科大学附属盛京医院老年病科,沈阳110004

出　　处：《实用药物与临床》2015年第3期260-264,共5页Practical Pharmacy and Clinical Remedies

基　　金：辽宁省科技计划项目(2011225020)

摘　　要：目的研究新诊断2型糖尿病患者外周血单核巨噬细胞SR-B1、ABCA1表达及胆固醇外流的变化,以及辛伐他汀治疗对上述指标的影响。方法采用Western印迹法及RT-PCR方法检测新诊断糖尿病患者(A1、B1组)、正常对照组(C组)及辛伐他汀治疗后(A2、B2组)外周血单核巨噬细胞SR-B1、ABCA1蛋白及mRNA表达、胆固醇外流率。结果新诊断糖尿病患者单核巨噬细胞SR-B1蛋白及mRNA表达各组间以及治疗前后比较差异无统计学意义(P>0.05)。ABCA1蛋白及mRNA表达明显降低(P<0.05),辛伐他汀治疗后B2组升高明显(P<0.05),但仍显著低于C组(P<0.05)。两个糖尿病组胆固醇外流率明显下降(P<0.05),A1、B1两组间差异无统计学意义(P>0.05)。治疗后的A2组胆固醇外流率轻度升高,但差异无统计学意义(P>0.05),B2组胆固醇外流率显著升高(P<0.05),但未达到C组水平(P<0.05)。巨噬细胞胆固醇外流率与ABCA1蛋白及mRNA表达密切相关(r1=0.752,r2=0.724,P<0.05)。结论新诊断2型糖尿病患者的外周血单核巨噬细胞胆固醇外流率较正常对照组明显下降,这种变化可能与转运体ABCA1表达下降有关。辛伐他汀治疗可能通过部分提高ABCA1表达从而增加胆固醇外流而起到抗动脉粥样硬化作用。Objective To learn the effects of diabetes status and simvastatin on cholesterol efflux from human peripheral blood monocytes（ PBM C）-derived macrophages,as well as the expression of scavenger receptor B1（ SR-B1）and ATP-binding cassette receptor A1（ ABCA1）. Methods Blood was collected from subjects with newly diagnosed type 2 diabetes（ T2 DM ： Group A1 and B1） and controls（ Group C）. Peripheral blood monocytes were differentiated for72 h into macrophages. The expression of SR-B1 and ABCA1 protein and mRNA were detected by Western blot and RT-PCR,respectively. Cholesterol efflux assays were performed at the same time. The experiments were repeated after twenty-four weeks simvastatin treatment（ Group A2-A1 without simvastatin; Group B2-B1 with simvastatin）. Results The expression of SR-B1 mRNA and protein was not significantly different among three groups,as well as that of simvastatin treatment（P〈0. 05）. In contrast,the expression of ABCA1 in macrophages from patients with T2 DM significantly reduced（P〈0. 05）. After twenty-four weeks simvastatin treatment,it was still lower than that of controls（P〈0. 05）,although it was upreglulated significantly（P〈0. 05）. In addition,cellular cholesterol efflux from macrophages to autologous serum significantly reduced in group A1 and B1,compared with group C（P〈0. 05）. In group A2,there was a slightly increase in macrophages cholesterol efflux,which was not significantly different compared with that in group A1（P〈0. 05）. Nevertheless,cholesterol efflux in group B2 ascended significantly compared with that in group B1（P〈0. 05）. The change of macrophage cholesterol efflux correlated with the expression of ABCA1 significantly（ r1 = 0. 752,r2 = 0. 724,P 0. 05）. Conclusion Cholesterol efflux reduced in macrophages of new diagnosis T2 DM,which may be correlated with down regulating of ABCA1. Simvastatin may plays a protective role through improving cholesterol efflux and upregulating ABCA1 expression.

关 键 词：胆固醇外流 SR-B1 ABCA1 辛伐他汀 

分 类 号：R587.1[医药卫生—内分泌]