Objective To explore the relationship of myocardial matrix metalloproteinase-3 (MMP-3), tissue inhibitor of metalloproteinase-1 (TIMP-1) with angiotensinⅡ (AngⅡ) in mice with Coxsackievirus myocarditis (VM).Methods Fifty-seven four to sixweek-old male Balb/c mice were divided into five groups randomly: group A, B, C and D. Mice in infected group (B～D, n =45) were inoculated intrapritoneally with 0.1ml of Coxsackievirus B3 (CVB3 Nancy strain). Group A (control, n = 12) were inoculated intrapritoneally with 0.1 ml of Hep-2' s solution. After 24h of inoculation, group C and D were treated with normal saline and fosinopril respectively. All mice were sacrificed on day 28. Myocardial collagen amount was measured by determination of hydroxyproline quantification,the AngⅡ contents in plasma was measured by radioimmunoassay, and the mRNA expression of MMP-3 and TIMP-1 were detected by reverse transcription-polymerase chain reaction (RT-PCR) .Results In group B and C, AngⅡ contents in plasma increased remarkably,the mRNA expression of MMP-3 was upregulated significantly and the mRNA expression of TIMP-1 was downregulated remarkably compared with those in group A (P＜0.05). The myocardial collagen amount in group B and group C increased significantly compared with controls. In group D, AngⅡ contents in plasma decreased remarkably, the mRNA expression of MMP-3 was downregulated significantly and the mRNA expression of TIMP-1 was upregulated remarkably compared with those in group B (P＜0.05). The myocardial collagen amount in group D decreased significantly compared with those in group B.Conclusion The mRNA expression of MMP-3and TIMP-1 was closely correlated with the changes of the AngⅡ contents in plasma of VM mice, and may contributes to myocardial collagen remodeling. These effects that the mRNA expression of MMP-3 was downregulated and TIMP-1 was upregulated significantly may be responsible for the effect of fusinopril on inhibiting the ang Ⅱ, and therefore the myocardial collagen amount decreased remarkably.%目的探讨柯萨奇病毒性心肌炎(VM)小鼠基质金属蛋白酶-3(MMP-3)及金属蛋白酶组织抑制因子-1(TIMP-1)与血管紧张素Ⅱ(AngⅡ)的关系.方法57只鼠龄4～6周Balb/c纯种雄性小鼠随机分为4组,对照组(A组,n=12)、模型组(B组,n=15)、假干预组(C组,n=15)、福辛普利组(D组,n=15).B～D组小鼠腹腔接种0.1 mL的Coxsakievirus B3(CVB3)病毒悬液建立VM模型,A组腹腔注射不含CVB3的0.1 mL Hep-2细胞冻溶液作为对照组.C组及D组于注射CVB3 24 h后分别给予生理盐水和福辛普利灌胃治疗,于第28天断颈处死小鼠,氯氨T法测定心肌胶原含量;放射免疫法检测血浆AngⅡ含量;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组及C组血浆AngⅡ含量显著增高,心肌MMP-3表达显著上调,TIMP-1表达显著下调,心肌胶原含量显著增高(与A组比较,P＜0.05);D组血浆AngⅡ含量显著下降,心肌MMP-3表达显著下调,TIMP-1表达显著上调,心肌胶原含量显著减少(与B组比较,P＜0.05).结论VM小鼠心肌MMP-3、TIMP-1mRNA表达与血浆AngⅡ变化密切相关,可能是导致心肌胶原重构的重要因素;福辛普利通过抑制AngⅡ的产生使心肌MMP-3mRNA表达显著下调、TIMP-1表达显著上调、心肌胶原含量显著减少.
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