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目的:探讨基质金属蛋白酶-3(MMP-3)及金属蛋白酶组织抑制因子-1(TIMP-1)在病毒性心肌炎(VM)小鼠中的作用及其与心肌胶原的关系。方法:62只鼠龄4~6周Balb/c纯种雄性小鼠随机分为,对照组(A组,n=8)、感染组(B组,n=54)2组。B组小鼠腹腔接种0.1ml的CVB3建立VM模型,A组腹腔注射0.1ml不含CVB3的Hep-2细胞冻溶液。B组于注射CVB3后第7、14、28、42天各处死8只小鼠,A组于第42天处死8只小鼠,心脏石蜡切片HE染色计算病理积分,免疫组化方法检测心肌型、型胶原的蛋白表达,逆转录-聚合酶链反应法(RT-PCR)检测心肌MMP-3、TIMP-1mRNA的表达。结果:B组心肌MMP-3表达上调,TIMP-1表达下调,以第14、28天时最显著;TIMP-1于第42天时表达上调;心肌型、型胶原沉积增多,以第28、42天时最显著(P<0.05);MMP-3的表达与病理积分呈正相关。结论:MMP-3/TIMP-1参与VM小鼠的病理过程,可能在心肌胶原重构中起重要作用。
AIM: To investigate the role of matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in viral myocarditis (VM) mice and its relationship with myocardial collagen. Methods: Sixty-two male Balb / c mice aged 4 to 6 weeks old were randomly divided into control group (group A, n = 8) and infected group (group B, n = 54). Group B mice were intraperitoneally inoculated with 0.1 ml of CVB3 to establish a VM model. Group A was intraperitoneally injected with 0.1 ml of frozen solution of Hep-2 cells without CVB3. In group B, 8 mice were sacrificed on the 7th, 14th, 28th and 42th days after injection of CVB3. Group A, 8 mice were sacrificed on the 42nd day. Pathological score was calculated by HE staining of the heart paraffin sections. Cardiomyocytes were detected by immunohistochemistry , Collagen type I protein, and reverse transcription-polymerase chain reaction (RT-PCR) were used to detect the expressions of MMP-3 and TIMP-1 mRNA in myocardium. Results: The expression of MMP-3 and TIMP-1 were down-regulated in group B, the most significant was on the 14th and 28th days. The expression of TIMP-1 was up-regulated on the 42nd day. The deposition of myocardial type and type collagen was increased. (P <0.05). The expression of MMP-3 was positively correlated with the pathological score. Conclusion: The involvement of MMP-3 / TIMP-1 in VM mouse pathological process may play an important role in cardiac collagen remodeling.