吲哚美辛抑制大鼠腹主动脉瘤基质金属蛋白酶9表达的研究

目的:研究吲哚美辛对大鼠腹主动脉瘤基质金属蛋白酶9(MMP-9)表达的抑制作用.方法:将腹主动脉瘤弹力蛋白酶灌注模型大鼠随机分为实验组和对照组,各8只.实验组皮下注射吲哚美辛(1.6 mg/d),对照组皮下注射生理盐水.观察两组动脉瘤的形成率和动脉壁的组织学改变,并应用免疫组织化学技术检测MMP-9在动脉壁中的表达.结果:灌注1周后实验组大鼠腹主动脉瘤形成率为0,对照组大鼠动脉瘤形成率为100%,两组差异有显著意义(P<0.05).2组大鼠弹力纤维染色均可见弹力纤维不连续,结构模糊不清,但对照组大鼠动脉中层弹力纤维层数明显减少,胶原纤维溶解现象较严重,实验组弹力纤维层的损伤较轻;实验组大鼠动脉壁组织MMP-9蛋白表达为弱阳性或阴性,对照组动脉瘤组织中MMP-9蛋白表达则明显增强.结论:吲哚美辛能降低MMP-9的表达,直接影响大鼠腹主动脉中膜弹力蛋白层的降解和退变过程,抑制实验性大鼠腹主动脉瘤的形成.

Indomethacin suppresses matrix metalloproteinase-9 expression in abdominal aortic aneurysm in rats

Objective:To investigate the mechanism by which indomethacin inhibits the expression of matrix metalloproteinase-9 in abdominal aortic aneurysm(AAA) in rats. Methods: Male Wistar rats underwent intraluminal perfusion of the abdominal aorta with 50 units of porcine pancreatic elastase followed by treatment with indomethacin (1.6 mg/d) subcutaneously (n=8) for 7 d or with normal saline(NS,n=8).Aortic wall elastin and collagen concentrations were measured with an imaging analysis system, and fixed aortic tissues were examined by light microscopy for inflammation. The expression of MMP-9 in aortic tissues was observed with immunohistochemistry technique. Results: AAAs developed in all NS treated rats and in none of indomethacin treated rats on d 7(P<0.01). The expression of MMP-9 protein in indomethacin treated aortic tissues was much less than that in control rats. Conclusion: Indomethacin can inhibit the development of experimental abdominal aortic aneurysm in vivo. This inhibition may be due to a selective blockade of elastolytic MMP-9 expression, leading to degradation of abdominal aortic elastin.