MMP-9、TIMP-1在实验性自身免疫性肌炎中的表达及甲基强的松龙的影响

目的探讨MMP-9在实验性自身免疫性肌炎(EAM)发病中的作用,以及甲基强的松龙对MMP-9、TIMP-1基因mRNA和蛋白表达的影响。方法应用RT-PCR及免疫组织化学技术,检测MMP-9、TIMP-1在EAM组、甲基强的松龙治疗组(EAMM组)和对照组大鼠外周血、脾脏、肌肉组织中的表达水平。结果(1)EAMM组大鼠发病程度低于EAM组,炎症细胞浸润和肌纤维坏死程度减轻。(2)MMP-9mRNA在EAM大鼠外周血、脾脏淋巴细胞中的表达上调;MMP-9蛋白在EAM组大鼠肌肉组织表达增加,与对照组比较,差异有显著性。EAMM组MMP-9mRNA及蛋白的表达均受到抑制,与EAM组比较差异有显著性。(3)与EAM组比较,EAMM组TIMP-1基因mRNA表达明显增加,同时TIMP-1蛋白表达上调更明显,差异有显著性。结论MMP-9表达增加可能与EAM发病有关;甲基强的松龙能减轻EAM发病程度,其作用机制可能与抑制MMP-9有关。

The expression of MMP-9 and TIMP-1 in EAM and the effects of methylprednisolone

Objective To investigate the effect of matrix metalloproteinase-9(MMP-9) in the attack of experimental autoimmune myositis(EAM) rats,and the effects of methylprednisolone on expressions of mRNA and protein of MMP-9 and TIMP-1. Methods The expression levels of MMP-9 and TIMP-1 in the peripheral blood,spleen lymphocytes and muscles were detected by using RT-PCR and immunohistochemistry techniques and was compared among EAM group,EAM with methylprednisolone treatment (EAMM) group and control group. Results (1) The degree of episode in EAMM group was lower than that of EAM group,and the infiltration of the inflammatory cells and the necrosis of the muscles were also mild in EAMM group. (2)There was significant upregulation of the expression of the MMP-9 gene mRNA in the lymphocytes of peripheral blood and spleen of EAM rats as compared with that of the control. Elevation of the expression of MMP-9 protein in rats muscles tissues of EAM group was observed obviously. However,the expression of the mRNA and the protein of MMP-9 was suppressed significantly in EAMM group compared with EAM group . (3)There was significant upregulation of the expression of the TIMP-1 gene mRNA of EAMM rats as compared with that of the EAM group. Elevation of the expression of TIMP-1 protein in rats muscles tissues of EAMM group was observed more obviously. Conclusion The upregulation of the expression of MMP-9 may be correlated with the onset of EAM. Methylprednisolone may relieve the degree of the pathology of EAM by the inhibition of MMP-9.