实验性自身免疫性肌炎中MMP—2，MMP—9，TIMP—1的表达及甲基强的松龙的影响

目的：探讨基质金属蛋白酶（MMP－2，MMP－9）及基质金属蛋白酶抑制剂（TIMP－1）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－2，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，研究MMP－2，MMP－9及TIMP－1在EAM组、甲基强的松龙治疗组（EAMM组）和对照组（NS组）大鼠外周血、脾脏、肌肉组织中的表达水平。结果：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。MMP－2，MMP－9 mRNA在EAM大鼠外周血、脾脏淋巴细胞中的表达上调；MMP－2，MMP－9蛋白在EAM组大鼠肌肉组织表达增加，与对照组相比差异有显著性。EAMM组MMP－2，MMP－9mRNA的表达及蛋白的表达均受到抑制，与EAM组比较差异有显著性。EAMM组TIMP－1基因mRNA及蛋白的表达上调，与EAM组相比差异有显著性。结论：MMP－2，MMP－9表达增加可能与EAM发病有关；TIMP－1可能参与了抑制免疫反应；甲基强的松龙能减轻EAM发病程度，其作用机制可能与MMP－2及MMP－9的表达下调、TIMP－1的表达上调有关。

Expression of MMP-2, MMP-9 and TIMP-1 and the effects of methylprednisolone in EAM]

OBJECTIVE: To study the function of MMP-2 (matrix metalloproteinase-2), MMP-9 (matrix metalloproteinase-9) and TIMP-1 (tissue inhibitor of metalloproteinase-1) in the pathogenesis of EAM (experimented autoimmune myositis) rats, and to evaluate the effect of methylprednisolone on the mRNA and protein expression of MMP-2, MMP-9 and TIMP-1. METHODS: The expression levels of MMP-2, MMP-9 and TIMP-1 in the peripheral blood, spleen lymphocytes and muscles were examined among the EAM group, EAMM group and control group by RT-PCR and immunohistochemical techniques. RESULTS: 1. The degree of episode in the EAMM group was lower than that in the EAM group. Also, the infiltration of the inflammatory cells and the necrosis of the muscles were milder in the EAMM group than those in the EAM group. 2. The mRNA expression of MMP-2 and MMP-9 in the lymphocytes of the peripheral blood and spleen and the protein expression of MMP-2 and MMP-9 in the muscle tissues all increased significantly in the EAM group compared with those of the control group. However, the mRNA and protein expression of MMP-2 and MM-9 was suppressed significantly in contrast with that in the EAM group. 3. The mRNA and protein expression of TIMP-1 in the EAMM group increased with statistical significance compared with that in the EAM group. CONCLUSION: The upregulation of the expression of MMP-2 and MMP-9 may be related with the onset of EAM. TIMP-1 may be involved in the suppression of immunoreaction. Methylprednisolone may reduce the pathological damages of EAM, and this protective mechanism may be due to the inhibited expression of MMP-2 and MMP-9 and promoted expression of TIMP-1.