虚拟组织学血管内超声评价吡格列酮抗动脉粥样硬化作用的实验研究

The anti-atherosclerotic effect of pioglitazone assessed by virtual histology intravascular ultrasound

目的:采用虚拟组织学血管内超声技术探讨吡格列酮抗动脉粥样硬化(As)及降低血栓事件发生的作用。方法:选取14只新西兰大白兔,以高脂饲养及腹主动脉球囊拉伤的方法复制As模型。喂养12周后随机分为吡格列酮组(吡格列酮每天10mg/kg,n=6)和对照组(n=6),并对两组兔行虚拟组织学血管内超声(VH-IVUS)检查,两组各选取40个斑块,测量相关参数,继续高脂喂养12周后,再次行VH-IVUS检查。最后药物诱发斑块血栓形成,处死并取出腹主动脉观察所选斑块血栓事件发生情况。对两组VH-IVUS相关参数及血栓事件进行比较。结果:经过12周的药物干预,吡格列酮组的TG、hs-CRP、MMP-9下降,HDL-C升高。VH-IVUS分析显示和对照组相比,吡格列酮组的坏死成分绝对面积[-0.10(0.00,0.10)vs.0.10(0.00,0.13)mm2,P<0.001]、坏死成分相对比例[(-2.35±3.11)vs.(1.87±4.62)%,P=0.012];钙化成分绝对面积[0.00(0.00,0.10)vs.0.10(0.00,0.10)mm2,P<0.001]、钙化成分相对比例[0.00(-3.12,0.14)vs.2.00(-0.19,3.19)%,P=0.002]明显减少。吡格列酮组的血栓事件发生率低于对照组(P<0.001)。结论:吡格列酮可以引起动脉粥样斑块的回缩,降低斑块血栓事件的发生,是新型的抗As药物。

Objective：To assess the effect of pioglitazone on anti-atherosclerotic and reduce the rate of atherothrombosis by virtual histology intravascular ultrasound（VH-IVUS） in a rabbit model. Methods： Athero- sclerotic plaques were induced in the abdominal aorta of 14 New Zealand white rabbits by a combination of a hy- perlipidemic diet and balloon endothelial denudations. After 12 weeks, 14 rabbits randomly divided into two groups： 6 rabbits continued the same diet, whereas 6 rabbits received pioglitazone（ 10rag. kg-1. d） in addition to the diet. Two group rabbits underwent VH-IVUS at 12 weeks ,40 plaque were selected respectively. Two group rabbits continued a hyperlipidemic diet for 12 weeks, then underwent VH-IVUS again. At the end, the rabbits underwent pharmaceutical triggering to induce atherothrombosis. We make a statistical analysis of the parameter received from VI-I-IVUS and atherothrombosis. Results： In the pioglitazone group after pharmacological inter- vention of 12 weeks, plasma triglyceride, high-sensitivity C-reactive protein and Matrix metallo preteinases-9 were significantly decreased, high density lipoprotein cholesterol was increase. In contrast to control animals, in the pioglitazone-treated group, the change of the absolute plaque content of necrotic core decreased[ -0. 10 （0. 00,0. 10） vs. 0. 10（0. 00,0. 13 ）mm2 ,P 〈0. 001 ], as well as the relative plaque content of necrotic core [ - 2. 35 ± 3.11 ） vs. （ 1.87 ± 4. 62） %, P = 0. 012 ], absolute dense-calcium [ 0. 00 （0. 00,0. 10 ） vs. 0. 10（0. 00,0. l 0 ）mm2, P 〈0. 001 ], relative dense-calcium [ 0. 00 （ - 3.12,0. 14） vs. 2.00 （ -0. 19,3.19 ） %, P =0. 002 ]. The incidence of thrombotic events had significantly decreased in the pioglitazone group compared with the control group（ P 〈0. 001 ）. Conclution ： Pioglitazone, as an novel anti-atherosclerotic agent, may induce regression of atherosclerotic plaque and reduce the rate of atherothrombosis.