阿托伐他汀抑制腹主动脉瘤基质金属酶9及核因子κB表达的实验研究
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广东省医科学基金资助(基金编号A2005505)


Treatment with Atorvastatin Suppresses the Development of Experimental Abdominal Aortic Aneurysms
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    摘要:

    目的研究阿托伐他汀对腹主动脉瘤基质金属酶9及核因子κB影响,探讨其临床应用价值。方法成年雄性WISTER大鼠24只,随机分为实验组和对照组,每组12只;分别皮下注射阿托伐他汀4 mg/(kg.d)和等容积的生理盐水。用弹力酶灌注法建立大鼠腹主动脉模型。观察两组动脉瘤形成率和动脉壁病理学改变。HE染色、弹力纤维EVG染色观察腹主动脉瘤组织学变化,逆转录聚合酶链反应检测动脉基质金属酶9及核因子κB mR-NA的表达水平,免疫组织化学分析基质金属酶9及核因子κB的蛋白表达水平。结果弹力酶灌注2周后实验组大鼠腹主动脉瘤形成率为20%,对照组动脉瘤形成率为90%,实验组动脉组织弹力纤维未见明显断裂消失等受损表现,仅有少量炎症细胞浸润及基质金属酶9及核因子κB的表达。对照组动脉壁组织弹力纤维严重受损,可见明显炎症细胞浸润,基质金属酶9及核因子κB的表达显著增高。结论阿托伐他汀能够降低动脉壁组织基质金属酶9及核因子κB的表达及炎症细胞的浸润,减少弹力纤维的降解,从而抑制实验性大鼠腹主动脉瘤的形成。

    Abstract:

    Aim To determine if treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors(statins) can influence the development of experimental abdominal aortic aneurysms(AAAs). Methods Twenty-four Wistar Rats were randomly divided into 2 equal groups(n=12).An animal model of AAAs was established by perfusion of the aorta with elastase,treated for 14 days with Atorvastatin 4 mg/(kg·d) or with NS alone.The expression of MMP-9 and NF-κB were observed in aortic tissue by immunohistochemistry staining or by RT-PCR. Result The incidence of AAAs was reduced by 70%(2 of 10 rats treated with atrovastatin vs.9 of 10 rats treated with vehicle ;P<0.05).The development of AAAs in vehicle-treated rats were accompanied by a dense transmural inflammatory response,and complete destruction of the elastic media.MMP-9 and NF-κB expression increase significantly in vehicle-treated rats.Inflammatory infiltration was less found in Atorvastatin-treated rat,and little MMP-9 and NF-κB expression in atrovastatin-treated rats. Conclusion Treatment with Atorvastatin reduced the development of elastase-induced experimental AAAs.The underlying mechanism was associated with structural preservation of aortic wall elastin and the presence of a chronic inflammatory response,there was a relative reduction in aortic wall expression of MMP-9and NF-κB,the effect is independent on serum cholesterol levels.

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许文平,邱健,李志梁,谢志泉,何柏身,梁爱琼.阿托伐他汀抑制腹主动脉瘤基质金属酶9及核因子κB表达的实验研究[J].中国动脉硬化杂志,2008,16(8):600~602.

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  • 收稿日期:2008-05-12
  • 最后修改日期:2008-08-12
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