摘要
目的:分析巨噬细胞、肝细胞及脂肪细胞ATP结合盒转运子A1(ABCA1)在兔动脉粥样硬化(AS)形成过程中对逆胆固醇转运(RCT)的作用,探讨及证明罗格列酮与辛伐他汀联用是否可以作为抗AS的新途径。方法:18只新西兰白兔随机分为3组,①对照组:单纯喂食高胆固醇饮食;②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);③罗格列酮+辛伐他汀组: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),辛伐他汀5mg/(kg·d)。6周后分别利用流式细胞术和液闪计数仪检测腹腔巨噬细胞、肝细胞和脂肪细胞的ABCA1表达量及对[3H]胆固醇转出率,利用酶法测定兔的血脂以及主动脉、肝脏、脂肪组织的胆固醇含量,并利用专业图像分析软件分析兔主动脉AS面积。结果:与对照组相比,罗格列酮组与罗格列酮+辛伐他汀组均提高血浆HDL-C、载脂蛋白A1(apoA1)水平,并显著增加3种细胞的ABCA1表达量及[3H]胆固醇转出率,同时使主动脉、肝脏、脂肪组织的胆固醇含量及主动脉AS面积明显减少,其中罗格列酮+辛伐他汀组的变化较罗格列酮组更加明显;在3组实验动物中,3种细胞的ABCA1表达量均分别与其[3H]胆固醇转出率呈正相关,同时3种组织的胆固醇含量则分别与3种细胞的[3H]胆固醇转出率呈负相关。结论:ABCA1是RCT的一个正性调节剂,罗格列酮+辛伐他汀通过明显上调ABCA1表达而促进体内RCT,从而发挥抗AS作用;罗格列酮与辛伐他汀联用更加有效的抑制AS的形成。
Objective：To investigae the effects of ATP-binding cassette transporter A1（ABCA1） in macrophages,adipocytes and hepatocytes on reverse cholesterol transport（RCT） during the formation of atherosclerosis（AS） in order to show the new anti-AS way of rosiglitazone combined with simvastatin in AS rabbits.Method：Eighteen rabbits were randomly divided into three groups（6 each）：control group（only high cholesterol diet for 6 weeks）,rosiglitazone group [the same high cholesterol diet plus rosiglitazone 0.5 mg·kg-1·d-1 for 6 weeks].Rosigitazone combined with simvastatin group [the same high cholesterol diet plus rosiglitazone 0.5 mg·kg-1·d-1 combined with simvastatin 5 mg/kg/d for 6 weeks].After 6 weeks,ABCA1 expression of macrophages,liver cells and fat cells 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 aorta,liver and fat tissues,and area of AS in aorta was calculated by professional image analysis software.Result：Compared with control group,rosiglitazone group and rosigitazone combined with simvastatin group showed high-density lipoprotein cholesterol（HDL-C） and apolipoprotein A1（apoA1） levels were increased,ABCA1 expressions and cholesterol efflux rates in the three cells were higher,cholesterol contents in the three tissues and AS area in aorta were decreased.Accordingly,the changes in rosigitazone combined with simvastatin group were more significantly than in rosiglitazone group.In three studied groups,ABCA1 expressions positively correlated with cholesterol efflux rates in the three cells respectively,but cholesterol contents in the three tissues negatively correlated with cholesterol efflux rates in the three cells respectively.Conclusion：ABCA1 is a positive regulator of RCT,and rosiglitazone combined with simvastatin significantly promotes RCT by up-regulating ABCA1 expressions thus attenuating atherosclerosis.
出处
《临床心血管病杂志》
CAS
CSCD
北大核心
2011年第1期66-70,共5页
Journal of Clinical Cardiology
基金
广东省自然科学基金(No:06024407)
