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The protective effect of rSjcystatin-Stefins on myocardial infarction of mice

李燕楠  Siyu Chen  Liying Xie  Lin Zuo  
【摘要】:Objective: The cystatins are a family of cysteine protease inhibitors which has been used in the treatment of inflammatory diseases because of its inhibitory effect on enzyme activity and negative immunoregulation.Myocardial infarction(MI) is an kind of aseptic inflammatory diseases which is lack of effective drugs for the treatment of inflammation.Whether cystatin family 1(Stefins) is involved in MI is not clear.Therefore, to explore the protective effect of recombinant rSjcystatin on MI of mice, cardiac structure and function, infiltration of inflammatory cells and serum inflammatory cytokine levels were measured in this experiment.Methods: 120 male C57 BL/6 J wild mice were randomly divided into four groups:(1) Sham group;(2) MI + PBS group;(3) MI + stefin group;(4) MI + dexamethasone(Dex) positive control group.The changes of cardiac function and the structure at the 1,3, 5, 7, 14 and 28 days post MI were observed by echocardiography, masson trichrome staining, the ratio of heart weight to body weight and the survival rate.The infiltration of inflammatory cells and sera inflammatory factors levels of TNF-α, IL-6, IL-10 and TGF-β at the 1,3, 5 and 7 days after MI were respectively observed by hematoxylin-eosin(HE) staining and enzyme-linked immunosorbent assay(ELISA).Results: Echo results showed that LVEF(left ventricular ejection fraction) and LVFS(left ventricular fractional shortening) in stefin treatment group and Dex treatment group were significantly higher than those in PBS group at the 28 th day after MI(P 0.05).Masson staining results showed that at the 28 th day post MI, the left ventricular wall thickness, infarct area and the diameter of left ventricle in stefin group and Dex treatment group were significantly improved compared with those in PBS group(P 0.05).HE staining showed that the inflammatory cells infiltration in PBS group was significantly higher than that in other groups at the same time point after MI.ELISA results showed that TNF-alpha and IL-6 representing classically activated macrophages decreased significantly in stefin group compared with that in PBS group at the 3 rd day after MI(P 0.05).Compared with PBS group, the levels of TGF-β representing alternatively activated macrophages, in stefin group and Dex group were significantly higher at the7 th day after MI(P 0.05); The serum IL-10 level in both groups were higher than that in PBS group.Conclusion: The recombinant protein rSjcystatin can significantly restrain the aseptic inflammatory response, delay myocardial remodeling and alleviate the deterioration of cardiac function post MI in mice.However, the potential mechanisms of anti-inflammatory therapy of rSjcystatin need to be further explored.

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