脂蛋白相关磷脂酶A_2与兔动脉粥样硬化的相关性研究

The relationship between lipoprotein-associated phospholipase A_2 and atherosclerosis in rabbits

目的建立新西兰白兔动脉粥样硬化不稳定斑块动物模型,探讨脂蛋白相关磷脂酶A2(Lp-PLA2)与兔动脉粥样硬化的关系。方法将16只健康雄性新西兰白兔随机分为2组:对照组8只,喂养普通饲料;模型组8只,喂养高脂饲料并行腹主动脉球囊拉伤手术。分别于第0(开始实验时计为0周)、5、15周采血测定血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、Lp-PLA2、白细胞介素-6(IL-6)与C反应蛋白(CRP)水平;第15周处死动物,取腹主动脉行病理分析。结果模型组动物第15周体重明显增加,血脂、Lp-PLA2明显升高(P<0.01);对照组各项指标无明显变化。与对照组相比,模型组血清TC、LDL-C、Lp-PLA2、CRP在第5周及15周显著升高(P<0.05);血清TG、IL-6在第15周明显升高(P<0.05)。病理分析显示模型组动物成功制备动脉粥样硬化不稳定斑块模型。结论采用高脂饮食加腹主动脉球囊拉伤术可成功制备动脉粥样硬化不稳定斑块动物模型,Lp-PLA2可作为判定动脉粥样硬化斑块不稳定的早期生物学标记物。

Objective To build an animal model of unstable atherosclerotic plaque and investigate the relationship between lipoproteinassociated phospholipase A2（Lp-PLA2） and atherosclerosis in the New Zealand white rabbits. Method The 16 healthy male New Zealand rabbits were randomly divided into 2 groups： 8 rabbits in control group with normal diet; 8 rabbits in high-fat-diet and vascular endothelial injury group that underwent balloon induced arterial wall injury and high fat diet. Fasting serum samples were collected for tests of total cholesterol（TC）, triglyceride（TG）, low density lipoprotein cholesterol（LDL-C）, high density lipoprotein cholesterol（HDL-C）, Lp-PLA2, interleukin-6（IL-6） and C-reactive protein（CRP） in the zero, 5 th and 15 th week. Meanwhile, the arteries of rabbits were studied under optical microscope for pathological changes in 15 th week. Result In the model group, the body weight increased significantly in15 th week, and the blood lipid and Lp-PLA2 increased significantly（P0.01）, but there were no significant changes in the control group. Compared with the control group, the serum levels of TC, LDL-C, Lp-PLA2, CRP in the model group were significantly increased in 5 th and 15 th week（P〈0.05）, and the serum TG and IL-6 levels were significantly increased in15 th week（P〈0.05）. Pathological analysis showed that atherosclerotic plaque model was successfully established in the model group. Conclusion An animal model of unstable atherosclerotic plaques can be built as based on high-fat-diet and balloon induced arterial wall injury. Lp-PLA2 can be used as an early biological marker to determine the instability of atherosclerotic plaque.