TNF-α和明胶酶在病毒性心肌炎中的动态变化

Dynamic changes of TNF-α and gelatinase on murine viral myocarditis model

目的:探讨TNF-α和明胶酶MMP-2、MMP-9在病毒性心肌炎(VMC)中的动态变化及其意义。方法:6周龄近交系雄性Balb/c小鼠随机分为对照组(n=35)和感染组(n=60),分别给予PBS和含10^(-5.69) TCID_(50)/mL的CVB3液0.1 mL注射,分别在第4、第10、第21、第30天各随机取8只小鼠处死并取血和心脏标本。ReedMuench法测定接种病毒滴度;HE染色后光镜观察心肌组织病理学改变;免疫组织化学法、Western blot和实时荧光定量PCR法分别检测心肌组织MMP-2、MMP-9蛋白及其mRNA的表达;ELISA法检测血清TNF-α的浓度变化。结果:与对照组比较,感染组血清TNF-α浓度明显升高(P<0.05),心肌组织MMP-2和MMP-9蛋白及其mRNA表达均显著增高(P<0.05)。MMP-2、MMP-9表达与心肌病理积分、TNF-α浓度均呈正相关。结论:在小鼠CVB3心肌炎中TNF-α及其下游产物MMP-2和MMP-9水平上调,可能参与VMC的病理生理过程。

Objective： To explore the dynamic changes and its meaning of TNF-α and gelatinase on themurine viral myocarditis model. Methods： Six-week-old inbred male mice were randomly assigned to control （n=35） and myocarditis group （n=60）. The myocarditis and the control groups were inoculated intraperitoneally with 0.1 mL 10-5.69 TCIDs0/mL CVB3 or vehicle （PBS） alone respectively. Eight mice were sacrificed at 4th day, 10th day, 21th day and 30th day after injection. The serum content of TNF-α was measured by ELISA. The myo- cardial levels of MMP-2 and MMP-9 were determined by Western blot, MMP-2 mRNA and MMP-9 mRNA were measured by RT-PCR. Results： Compared with the control group, the protein and mRNA expression of MMP-2 and MMP-9 in the myocardium and the serum contents of TNF-α were significantly increased in myocarditis group （P〈0.05）. Conclusion： The expression of TNF-α and its downstream production MMP-2 and MMP-9 are increased in mice with acute viral myocarditis, and it may be involved in the pathogenesis of viral mvocarditis.