四环素抑制实验性大鼠腹主动脉瘤形成的初步研究

Suppression of experimental abdominal aortic aneurysm by tetracycline: a preliminary study

目的 研究四环素对实验性大鼠腹主动脉瘤形成的作用。方法 建立大鼠腹主动脉瘤弹力蛋白酶灌注模型 ,随机分为实验组 (10只 )皮下注射四环素 (2 5mg/d) ,对照组 (10只 )皮下注射生理盐水。观察两组动脉瘤形成率和动脉壁组织学改变 ,并应用免疫组织化学和分子原位杂交技术检测基质金属蛋白酶 2和 9的表达。结果 灌注 2周后实验组大鼠腹主动脉瘤形成率 10 % ,对照组大鼠动脉瘤形成率为 10 0 % ,两组差异有显著意义 (P <0 0 5 )。实验组大鼠动脉壁组织MMP 2、MMP 9蛋白表达为弱阳性或阴性 ,对照组动脉瘤组织中两者表达明显增高。原位杂交检测结果表明两组mRNA表达强度无明显差异。结论 四环素能够降低基质金属蛋白酶 2和 9的表达 ,从而减低动脉壁组织弹力纤维的降解 。

ObjectiveTo investigate the mechanism by which tetracycline inhibits the development of experimental abdominal aortic aneurysms (AAA).MethodsMale Wistar rats underwent intraluminal perfusion of the abdominal aorta with 50 units of porcine pancreatic elastase followed by treatment for 14 days with tetracycline (25?mg/day, subcutaneously; n=10) or with NS alone (n=10). Aortic wall elastin and collagen concentrations were measured with image analysis system and fixed aortic tissues were examined by light microscopy for inflammation. The expression of MMP-2 and MMP-9 were observed in aortic tissues using immunohistochemistry and molecular in situ histohybridization technique. Results AAAs developed in all NS-treated rats, and only 1/10 of tetracycline-treated rats at 14 days(P<0.01). The positive expression of MMP-2 and 9 protein in tetracycline treated aortic tissues were much less than that in control rats. ConclusionsTreatment with tetracycline inhibits the development of experimental abdominal aortic aneurysms in vivo. This inhibition may due to a selective blockade of elastolytic MMP expression.