辛伐他汀对兔动脉粥样硬化脂蛋白相关的磷脂酶A2蛋白表达的影响
首发时间:2008-12-30
摘要:目的:观察辛伐他汀治疗对兔动脉粥样硬化中磷脂酶A2蛋白表达及活性的影响。方法:将24只雄性新西兰兔随机分为3组:对照组(n=8),饲喂基础饲料12周;AS组(n=8),饲喂高脂饲料12周;辛伐他汀组(n=8),饲喂高脂饲料8周,继之以含有辛伐他汀(5mg/kg)的高脂饲料饲喂4周。分别于基线水平、实验第4、8、12周取血,并于实验结束时取主动脉检测血浆和主动脉粥样硬化病变处Lp-PLA2的蛋白表达及活性和AS病变程度。结果:(1)AS组兔血浆和主动脉内Lp-PLA2活性明显增加,AS病变处Lp-PLA2蛋白表达也明显增加。而辛伐他汀治疗4周可以明显降低血浆及主动脉内Lp-PLA2的活性,同时还可明显抑制AS斑块处Lp-PLA2蛋白的表达;(2)辛伐他汀可明显抑制AS兔主动脉内膜增生;(3)与AS组相比,辛伐他汀可明显降低动脉粥样硬化斑块内巨噬细胞数量,减少脂质沉积,同时增加平滑肌细胞含量。结论:兔主动脉粥样硬化病变处Lp-PLA2蛋白表达增加、酶活性明显增强。辛伐他汀治疗不仅可以明显降低兔主动脉粥样硬化病变处Lp-PLA2的活性及蛋白的表达,同时有效降低血循环中Lp-PLA2的活性。此外,辛伐他汀还可调节动脉粥样硬化斑块内的主要成分,稳定斑块。
关键词: 脂蛋白相关的磷脂酶A2 辛伐他汀 动脉粥样硬化 炎症
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The Effects of Simvastatin on the Expression of Lipoprotein Associated Phospholipase A2 in the Atherosclerotic Rabbits
Abstract:[objective] To investigate the effects of simvastatin on the expression and activity of Lp-PLA2 in the atherosclerotic rabbits. [Methods] 24 four months male New Zealand White (NZW) rabbits were randomly assigned to three groups: control group (n=8), fed a normal diet for 12 weeks; atherosclerosis (AS) group, fed a high-cholesterol diet for 12 weeks; simvastatin group, fed a high-cholesterol diet for 8 weeks and the diet containing simvastatin (5mg/kg) for additional 4 weeks. Blood samples were taken at times of 0, 4, 8, 12 weeks and the aortic samples were obtained at the end of the study, which was to determined plasma and aortic Lp-PLA2 activity and Lp-PLA2 expression in atherosclerotic plaque and composition of aortic plaques. [Results] (1) Lp-PLA2 activity of plasma and atherosclerotic aortas increased significantly of AS groups rabbits compared with control group. Positive in immunocytochemistry for Lp-PLA2 were detected in AS rabbits. However, simvastatin reduced Lp-PLA2 activity in rabbit plasma and aortas. Moreover, simvastatin treatment inhibited the protein expression of Lp-PLA2 in lesions. (2) Simvastatin treatment significantly reduced intima-media ratio. (3) Compared with AS group, simvastatin decreased the macrophage content and extracellular lipid deposition in the cross-sectional area of lesion. On the other hand , the smooth muscle cells were significantly increased by treatment. [Conclusions] The expression and enzyme activity of Lp-PLA2 are increased in atherosclerosis lesion. Simvastatin treatment significantly reduced Lp-PLA2 activity in rabbit plasma and aortas as well as the protein expression in AS lesion. Furthermore, simvastatin exerts the anti-inflammatoy roles and stabilized atheromatous plaques.
Keywords: Lipoprotein associated phospholipase A2 Simvastatin Atheroclerosis Inflammation
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