The Function And Molecular Mechanism Of JNK Pathway In Nicotine-related Abdominal Aortic Aneurysms

Background:Aortic aneurysm is a common disease in elders which has been the 13^th death reason;smoking is the only one risk factor of aneurysm that can be controlled,as the principal component of cigarette,nicotine has been reported can induce aneurysm.In our past research,we have found that nicotine with low dose AngII can induce aortic aneurysm in male C57/BL6J of 10-12 month old,additionally,the expression of P-JNK?MMP-2?MMP-9 can be upregulated.In vitro,nicotine can upregulate the expression of MMP-2?MMP-9?VCAM-1 in RAW264.7 and MOVAS cells in a dose-dependent manner.All these researches implied us that JNK may take part in the formation of aortic aneurysm and the expression of MMPs and CC inflammation factors.Objective:On the basis of our previous study,the purpose of this study was to elucidate the role of JNK in nicotine-related aortic aneurysm by treated with the inhibition of JNK pathway,furthermore,the molecular mechanism underlying.Method:Divided 40 male C57/BL6J into two group:one treated whit nicotine?4mg.kg-1.d?plus AngII?0.72mg.kg-1.d?,another group treated with the co-treatment plus SP600125?30mg/kg?.After 4 weeks,anatomic the mices and take the artery from the aortic arch to the abdominal aorta and renal artery bifurcation,store the tissues in liquid nitrogen for biochemical assay and in formalin for immuno histochemistry assay.Statistics on the rate of tumor formation in two groups of mice,the expression of MMP-2?MMP-9?MCP-1 and RANTES via Western blot and immunohistochemical.Results:Compared with nicotine plus AngII co-treated group,the incidence of aneurysm of group with the co-treatment plus SP600125 is obviously depressed.As the result of immunohischemical,the positive stainings of MMP-2?MMP-9 are significantly increased in nicotine-plus AngII group,especially in the area around the rupture site of aorticmedia,but in the triple-drug group,the positive stainings are restrained.The result of Western blot can detect the same conclusion.Conclusion:SP600125 as an inhibiton of JNK pathway may play an important role in the formation of nicotine-related aortic aneurysm via regulate the expression of MMPs and inflammation chemokine factors.