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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 analyze the effect of ATP binding cassette transporter A1 (ABCA1) in macrophages, hepatocytes and adipocytes on the development of reverse cholesterol transport (RCT) during the development of atherosclerosis (AS) in rabbits, and to investigate and demonstrate the role of rosiglitazone Can Simvastatin be used as a new anti-AS pathway. Methods: Eighteen New Zealand white rabbits were randomly divided into three groups: ① control group: fed with high cholesterol diet alone; ② rosiglitazone group: Rosiglitazone 0.5 mg / kg · d); ③ rosiglitazone + simvastatin group: Rosiglitazone 0.5 mg / (kg · d), simvastatin 5 mg / (kg · d) ). After 6 weeks, the expression of ABCA1 and the rate of [3H] cholesterol in peritoneal macrophages, hepatocytes and adipocytes were detected by flow cytometry and liquid scintillation counting respectively, Liver, adipose tissue cholesterol content, and the use of professional image analysis software analysis of rabbit aorta AS area. Results: Compared with the control group, rosiglitazone group and rosiglitazone + simvastatin group increased plasma levels of HDL-C and apolipoprotein A1 (apoA1), and significantly increased ABCA1 expression in three kinds of cells [3H] cholesterol transfer rate, while the aorta, liver, adipose tissue cholesterol content and aortic AS area decreased significantly in which rosiglitazone + simvastatin group changes more obvious than the rosiglitazone group; in The ABCA1 expression levels of three kinds of cells in three groups of animals were positively correlated with their [3H] cholesterol turnover rate, while the three groups of cholesterol levels were negatively correlated with the [3H] cholesterol turnover rates of the three kinds of cells . CONCLUSION: ABCA1 is a positive regulator of RCT. Rosiglitazone and simvastatin exert an anti-AS effect by up-regulating ABCA1 expression in vivo and in vivo. Rosiglitazone and simvastatin combined with more effective inhibition AS formation.