阿托伐他汀对动脉粥样硬化兔氧化应激/炎症反应的影响
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湖南省自然科学基金重点课题(09JJ3073);;长沙市科技计划重点项目(K0802106-31)


Effect of Atorvastatin on Oxidative Stress/Inflammatory Response in Rabbits with Atherosclerosis
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    目的通过研究氧化应激和炎症反应探讨阿托伐他汀治疗动脉粥样硬化的非调脂作用机制。方法以高脂饲料和免疫刺激方法制备动脉粥样硬化家兔模型,给予0.435 mg/(kg.d)阿托伐他汀混悬液治疗1个月,观察家兔血清超氧化物歧化酶活性、丙二醛和氧化型低密度脂蛋白含量以及血凝素样氧化型低密度脂蛋白受体1、主动脉血管细胞黏附分子1、细胞间黏附分子1、单核细胞趋化蛋白1基因和蛋白表达的变化。结果与正常对照组比较,动脉粥样硬化模型组家兔血清超氧化物歧化酶活性显著下降(P<0.01),血清丙二醛、氧化型低密度脂蛋白含量明显升高(P<0.01);主动脉血凝素样氧化型低密度脂蛋白受体1、血管细胞黏附分子1、细胞间黏附分子1、单核细胞趋化蛋白1的mRNA和蛋白表达明显升高(P<0.05或P<0.01)。与模型组比较,阿托伐他汀组家兔血清超氧化物歧化酶活性显著升高(P<0.01),血清丙二醛、氧化型低密度脂蛋白含量均显著下降(P<0.01),主动脉血凝素样氧化型低密度脂蛋白受体1、血管细胞黏附分子1、细胞间黏附分子1、单核细胞趋化蛋白1的mRNA和蛋白表达明显下调(P<0.05或P<0.01)。结论阿托伐他汀具有抗氧化应激和炎症反应的作用,从而保护血管内膜,发挥治疗动脉粥样硬化的作用。

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    Aim To study the non-lipid mechanisms of atorvastatin treating atherosclerosis by observing the changes of oxidative stress and inflammatory response. Methods The rabbit model of atherosclerosis were prepared by feeding the high fat diet and immune stimulation,then 0.435 mg/(kg·d) suspension of atorvastatin was given for 1 month.It was observed for the rabbit serum superoxide dismutase(SOD) activity,malondialdehyde(MDA) and oxidized low density lipoprotein(ox-LDL) levels and lectin-like oxidized low density lipoprotein cholesterol receptor-1(LOX-1),vascular cell adhesion molecule-1(VCAM-1),intercellular adhesion molecule-1(ICAM-1),monocyte chemoattractant protein-1(MCP-1) gene and protein expression. Results Compared with the control group,rabbit serum SOD activity was significantly decreased(P<0.01),serum MDA,ox-LDL was significantly higher(P<0.01);mRNA and protein expression of aortic LOX-1,VCAM-1,ICAM-1,and MCP-1 were significantly increased(P<0.05 or P<0.01) in atherosclerosis model group.Compared with model group,rabbits serum SOD activity was significantly increased(P<0.01),serum MDA,ox-LDL levels were significantly decreased(P<0.01);mRNA and protein expression of aortic LOX-1,VCAM-1,ICAM-1,and MCP-1 were significantly lower in atorvastatin group(P<0.05 or P<0.01). Conclusions Atorvastatin possesses anti-oxidative stress and inflammatory response,thereby it can protect the vascular endothelium and play a therapeutic role in atherosclerosis.

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葛金文,刘吉勇,朱惠斌,陈懿,王国佐.阿托伐他汀对动脉粥样硬化兔氧化应激/炎症反应的影响[J].中国动脉硬化杂志,2011,19(12):979~983.

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  • 收稿日期:2011-04-06
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