罗格列酮对动脉粥样硬化兔逆胆固醇转运的促进作用观察

Mechanism of rosiglitazone in promoting the reverse cholesterol transport in atherosclerotic rabbits

目的探讨在兔动脉粥样硬化(AS)形成过程中,罗格列酮对ATP结合盒转运子A1(ABCA1)及逆胆固醇转运(RCT)的影响及其抗AS的机制。方法12只新西兰兔随机均分为对照组(单纯喂食高胆固醇饮食6周)、罗格列酮组[在单纯高胆固醇饮食的基础上,予以灌服罗格列酮0.5mg/(kg·d)6周]。分别利用流式细胞术及液相闪烁计数法检测外周血单核细胞、腹腔巨噬细胞、皮下脂肪细胞、肝细胞的ABCA1表达量及[3H]胆固醇转出率,应用酶法测定血脂及肝组织、脂肪组织、升主动脉的胆固醇含量,并利用专业图像分析软件分析兔主动脉AS面积。结果实验6周后,罗格列酮组及对照组血浆非高密度脂蛋白胆固醇(NHDL-C)、高密度脂蛋白胆固醇(HDL-C)、载脂蛋白A1(apoA1)水平均较0周时显著升高(P<0.01),且罗格列酮组血浆HDL-C、apoA1水平显著高于对照组(P<0.05或P<0.01),但NHDL-C水平两组无明显差异(P>0.05)。6周时与对照组比较,罗格列酮组单核细胞、腹腔巨噬细胞、皮下脂肪细胞、肝细胞的ABCA1表达量增加(P<0.01),腹腔巨噬细胞、皮下脂肪细胞、肝细胞的[3H]胆固醇转出率增加(P<0.01或P<0.05),主动脉、脂肪组织、肝组织的胆固醇含量及主动脉AS面积明显减少(P<0.01或P<0.05)。结论ABCA1是RCT的一个正性调节剂;罗格列酮可通过上调单核/巨噬细胞、脂肪细胞及肝细胞ABCA1的表达促进体内RCT,从而发挥抗AS作用。

Objective To investigate the effects and anti-atherosclerotic mechanism of rosiglitazone on the expression of ATP-binding cassette transporter A1 （ABCA1） and reverse cholesterol transport （RCT） in atherosclerotic rabbits. Methods Twelve rabbits were randomly divided into two groups （6 each）： control group （only high cholesterol diet for 6 weeks）, rosiglitazone group [high cholesterol diet plus rosiglitazone 0.5mg/（kg·d） for 6 weeks]. ABCA1 expression and [3H] cholesterol efflux rates were evaluated by flow cytometry and liquid scintillation spectrometry, respectively. Enzymatic methods were used to assay serum lipids levels and cholesterol contents in tissues, and the atherosclerotic area of aorta was calculated by professional image analysis software. Results For the rabbits of both control and rosiglitazone group, the serum levels of high-density lipoprotein cholesterol （HDL-C）, non-high-density lipoprotein cholesterol （NHDL-C） and apolipoprotein A1 （apoA1） significantly went up when they took their cholesterol rich diet for 6 weeks （P0.01）. HDL-C and apoA-1 levels were higher in rosiglitazone group than that in control group at the 6th week （P0.05 and P0.01）, while no significant difference was found in NHDL-C level and weight between the two groups （P0.05）. Compared with control group, the ABCA1 expressions in monocytes, peritoneal macrophages, adipocytes and hepatocytes, as well as the cholesterol efflux rates in peritoneal macrophages, adipocytes and hepatocytes increased significantly （P0.01 or P0.05） in rosiglitazone group at the 6th week. Compared with control group, HDL-C and apoA1 levels went up and cholesterol contents in aorta, adipose and liver tissues and atherosclerosis area of aorta decreased in rosiglitazone group （P0.01 or P0.05）. Conclusion ABCA1 is a positive regulator of RCT, and rosiglitazone promotes RCT by up-regulating ABCA1 expressions in monocytes/macrophages, adipocytes and hepatocytes, thus attenuating atherosclerosis.