基质金属蛋白酶及其抑制剂在风湿性心脏病二尖瓣病变组织中的表达

Expression of matrix metallproteinases and their tissue inhibitors in mitral valve with rheumatic heart disease

目的探讨基质金属蛋白酶（MMPs）及其抑制剂（TIMPs）在风湿性心脏病（RHD）二尖瓣膜病理改变中的作用及其机制。方法实验组为成人RHD患者二尖瓣16例，对照组为同期意外死亡的无心脏病变的成人二尖瓣7例。经HE染色及电镜观察两组形态学和超微结构变化，采用逆转录-聚合酶链反应（RT-PER）和免疫组织化学染色（SABC法）测定MMP-2、MMP-13、TIMP-1及TIMP-2在二尖瓣组织的mRNA含量和蛋白表达。结果实验组为风湿性病理改变，对照组结构基本正常。实验组MMP02、13及TIMP-1、2的mRNA表达分别为0．96±0．27、0．93±0．38、0．87±0．32、0．94±0．37，较对照组均明显增加（P〈0．05）；其MMP-2、13及TIMP-1、2蛋白表达亦明显高于对照组。结论RHD患者二尖瓣膜中MMPs／TIMPs表达增强，可能参与二尖瓣细胞外基质（ECM）的重构，是其风湿性改变的重要分子机制之一。

Objective To explore the pathological role and mechanisms of matrix metalloproteinases （MMPs） and their tissue inhibitors （TIMPs） in mitral valve of patients with rheumatic heart disease （RHD）. Methods Experimental group was composed of 16 samples of rheumatic mitral valves, while control group consisted of 7 normal mitral valves from adults who were died accidentally without cardiovascular diseases. Tissue samples were investigated by hematoxylin and eosin stain ,reverse transcription polymerase chain reaction （RT-PCR） , immunohistochemistry and transmission electron microscopy （TEM）. Results Pathological figures and microstructures of rheumatic transformation in experimental group were showed dramatically, while the structures were basically normal in, control group. The expression levels of MMP-2,13 and TIMP-1,2 mRNA were increased significantly in RHD group compared with control group （ P 〈 0.05）. Conclusion The up-regulation of the expression of MMPs/TIMPs system may involved in the remodeling of extracellular matrix of mitral valve, and may be one of the important molecular mechanisms in its rheumatic pathologic developing process.