Zhao Sihai, Zhang Chunfang, Lin Yan, Yang Peigang, Yu Qi, Chu Yonglie, Yang Penghui, Fan Jianglin, Liu Enqi
Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, 710061, China.
Thromb Res. 2008;123(2):281-7. doi: 10.1016/j.thromres.2008.04.011. Epub 2008 Jun 17.
Thiazolidinedione (TZD) is widely used a drug for the treatment of type 2 diabetes and protects against cardiovascular events in human. However, it is not clear whether TZD can directly inhibit the progression of atherosclerosis. To test the hypothesis whether administration of TZD could reduce the development of atherosclerosis, we studied the effects of rosiglitazone on aortic atherosclerosis of rabbits fed a cholesterol diet.
Male Japanese White rabbits were fed a diet containing either 0.3% cholesterol diet (control group, n=10) or 0.3% cholesterol with rosiglitazone (TZD-treated group, n=12) for 16 weeks. We compared the plasma lipids and the extent of aortic atherosclerosis between two groups.
TZD treatment significantly resulted in the reduction of aortic atherosclerosis by 21% in the aortic arch (p<0.01), 20% in the thoracic aorta (p=0.14), and 28% in the abdominal aorta (p=0.25), without affecting the plasma levels of triglycerides, total cholesterol, high-density lipoprotein cholesterol, glucose and insulin. Immunohistochemical staining showed that the cellular components (macrophages and smooth muscle cells) of the lesions of TZD-treated rabbits were unchanged compared to those of control rabbits. In addition, TZD treatment also led to dramatic improvement of fatty liver in cholesterol-fed rabbits. Our results suggest that the activation of PPARgamma can be beneficial for the treatment of atherosclerosis and fatty liver independent upon the improvement of plasma lipids and glucose metabolism.
噻唑烷二酮（TZD）是一种广泛用于治疗2型糖尿病的药物，对人类心血管事件具有保护作用。然而，TZD是否能直接抑制动脉粥样硬化的进展尚不清楚。为了验证TZD给药是否能减少动脉粥样硬化的发展这一假设，我们研究了罗格列酮对喂食胆固醇饮食的兔子主动脉粥样硬化的影响。
雄性日本白兔分别喂食含0.3%胆固醇的饮食（对照组，n = 10）或含0.3%胆固醇及罗格列酮的饮食（TZD治疗组，n = 12），持续16周。我们比较了两组的血脂和主动脉粥样硬化程度。
TZD治疗显著使主动脉弓处的主动脉粥样硬化减少21%（p < 0.01），胸主动脉处减少20%（p = 0.14），腹主动脉处减少28%（p = 0.25），且不影响甘油三酯、总胆固醇、高密度脂蛋白胆固醇、血糖和胰岛素的血浆水平。免疫组织化学染色显示，与对照兔相比，TZD治疗兔病变的细胞成分（巨噬细胞和平滑肌细胞）没有变化。此外，TZD治疗还使喂食胆固醇的兔子的脂肪肝得到显著改善。我们的结果表明，PPARγ的激活对动脉粥样硬化和脂肪肝的治疗有益，且独立于血脂和葡萄糖代谢的改善。
