卡维地洛对急性病毒性心肌炎小鼠TNF-α,MMP-3及TIMP-1表达的影响

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目的:研究卡维地洛对急性柯萨奇B3(CVB3)病毒性心肌炎小鼠的肿瘤坏死因子-α(TNFα-)、基质金属蛋白酶-3(MMP-3)及组织型基质金属蛋白酶抑制因子-1(TIMP-1)表达水平的影响。方法:将80只雄性Balb/C小鼠随机分为3组:正常对照组(n=20),心肌炎组(n=30),卡维地洛组(n=30)。后2组经腹腔接种CVB3诱发急性VMC,感染24 h后,卡维地洛组小鼠灌胃给予卡维地洛10 m·gkg-1·d-1,连续14 d。于接种d 14随机从各组抽取8只小鼠取血后处死并留取心脏等标本。比较干预组与对照组的心肌病理改变,采用ELISA法检测血清TNFα-,采用RT-PCR法检测心肌MMP-3及TIMP-1 mRNA的表达。结果:与心肌炎组比较,卡维地洛组心肌病理损伤明显减轻;与正常组比较,病毒性心肌炎小鼠血清TNFα-明显升高,心肌MMP-3表达明显上调,TIMP-1表达明显下调;卡维地洛干预后小鼠血清TNFα-明显下降,心肌MMP-3表达明显下调,TIMP-1表达明显上调。结论:卡维地洛通过抑制TNFα-水平、下调MMP-3的表达、以及上调TIMP-1的表达,减轻心肌炎小鼠的心肌损害。 Objective: To investigate the effects of carvedilol on the expression of tumor necrosis factor-α (TNFα-), matrix metalloproteinase-3 (MMP-3) and tissue inhibitor of matrix metalloproteinase-1 in mice with viral myocarditis induced by Coxsackievirus B3 -1 (TIMP-1) expression levels. Methods: Eighty male Balb / C mice were randomly divided into three groups: normal control group (n = 20), myocarditis group (n = 30) and carvedilol group (n = 30). The latter two groups were intraperitoneally inoculated with CVB3 to induce acute VMC. After 24 hours of infection, the carvedilol group mice were intragastrically given 10 mg · kg-1 · d-1 of carvedilol for 14 days. Eight mice were randomly selected from each group after inoculation d 14 to take blood and sacrificed heart samples. The myocardial pathological changes of the intervention group and the control group were compared. The serum TNFα- was detected by ELISA, and the expression of MMP-3 and TIMP-1 mRNA was detected by RT-PCR. Results: Compared with the myocarditis group, the myocardial pathological changes in the carvedilol group were significantly reduced. Compared with the normal group, the levels of TNFα in the myocardium of the mice with viral myocarditis were significantly increased, the expressions of MMP-3 and TIMP-1 were significantly down-regulated in the myocardium, After intervention with carvedilol, the level of TNF-α in serum was significantly decreased, the expression of MMP-3 in myocardium was down-regulated and the expression of TIMP-1 was up-regulated. Conclusion: Carvedilol ameliorates myocardial damage in mice with myocarditis by inhibiting the TNFα level, down-regulating the expression of MMP-3 and up-regulating the expression of TIMP-1.
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