吡格列酮对高脂饮食兔主动脉血管内皮细胞黏附分子-1表达的影响

Effects of pioglitazone on the expression of aortic VCAM-1 in rabbits fed with high-fat diets

目的探讨吡格列酮对高脂饮食下兔主动脉血管内皮细胞黏附分子(VCAM)-1表达的影响。方法设立正常饮食、高脂饮食及高脂饮食加吡格列酮干预3组,通过比较主动脉病理形态学改变、血脂的变化、VCAM-1分子的表达进行研究,采用苏木素-伊红染色用于主动脉病理形态学观察,采用免疫组织化学检测兔主动脉上VCAM-1的表达。结果吡格列酮能减轻高脂饮食所致的内膜增厚和平滑肌增生。吡格列酮还能明显升高高密度脂蛋白胆固醇(HDL),对总胆固醇(TC)、低密度脂蛋白胆固醇(LDL)、甘油三酯(TG)无明显影响。高脂饮食刺激兔主动脉VCAM-1的表达增加,吡格列酮能显著减轻这种作用(0.78±0.16vs0.42±0.11,P<0.01)。结论吡格列酮能减轻高脂饮食兔主动脉VCAM-1的表达,其作用的机制可能与其干扰核转录因子有关。

Objective To exam the effects of Pioglitazone on the expression of aortic VCAM-1 in rabbits fed with high-fat diets. Methods Fifteen healthy male New Zealand rabbits were randomly divided into three groups to receive 8 weeks of normal diet （control group, n=5）, high cholesterol diet （high-cholesterol group, n=5） or high cholesterol diet plus 3 mg·kg·d^-1 pioglitazone added from the fourth week of cholesterol diet （pioglitazone treatment group, n=5）. The pathomorphology of rabbit aorta was studied with haematoxylin-eosin staining, and expression of VCAM-1 in rabbit aorta detected using immunohistochemistry. Results Pioglitazone appeared to decrease intimal hyperplasia and smooth muscle cell proliferation in aorta of rabbits fed with high-cholesterol diet. Furthermore, pioglitazone signifi- cantly improved the level of high density lipoprotein but showed no effects on TG, TC and LDL-C. Expression of aortic VCAM-1 was also markedly reduced with Pioglitazone treatment as compared with rabbits on high-fat diet alone （0.42±0.11 vs 0.78±0.16,P〈0.01）. Conclusion Pioglitazone may inhibit the upregnlation of VCAM-1 in aorta of hy-percholesterolemic rabbits, possibly resulting from its effects on nucleus transcription factors. These findings provide new insights into a potentially novel anti-atherosclerotic pathway by thiazolidinediones.