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  

Treatment with Atorvastatin Suppresses the Development of Experimental Abdominal Aortic Aneurysms

作　　者：许文平[1] 邱健[2] 李志梁[3] 谢志泉[2] 何柏身[1] 梁爱琼[2] 

机构地区：[1]中国人民解放军驻香港部队医院,广东省广州市518048 [2]广州军区广州总医院心内科,广东省广州市510010 [3]南方医科大学附属珠江医院心内科,广东省广州市510040

出　　处：《中国动脉硬化杂志》2008年第8期600-602,共3页Chinese Journal of Arteriosclerosis

基　　金：广东省医科学基金资助(基金编号A2005505)

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。Aim To determine ff 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 peffusion of tile 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 Tile incidence of AAAs was reduced by 70% （2 of 10 rats treated with atrovastatin [20% ]vs. 9 of 10 rats treated with vehicle [90% ] ; P 〈 0.05 ）. The development of AAAs in vehicle-treated rats were accompanied by a dense transmittal imqanunatory response, and complete destruction of the elastic media. MMP-9 and NF-κB expression increase significandy 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 elasfin and the presence of a chronic inflammatory response, there was a relative reduction in aortic wall expression of MMP-gand NF-κB, the effect is independent on serum cholesterol levels.

关 键 词：病理学与病理生理学 腹主动脉 阿托伐他汀 大鼠 基质金属酶9 核因子ΚB 

分 类 号：R363[医药卫生—病理学]