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  

Effect of carvedilol on expression of TNF-α,MMP-3 and TIMP-1 in mice with acute viral myocarditis

作　　者：李秀清 周娜丹[2] 李岳春[2] 

机构地区：[1]上海市崇明县庙镇人民医院内科,上海202153 [2]温州医学院附属第二医院心内科,温州325027

出　　处：《中国新药杂志》2011年第8期736-739,共4页Chinese Journal of New Drugs

基　　金：浙江省自然科学基金(Y2100551);温州市科技局基金(Y20080124)

摘　　要：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 determine the effect of carvedilol on expression of TNF-α,MMP-3 and TIMP-1 in mice with acute viral myocarditis induced by coxsackievirus B3 virus（CVB3） infection.Methods： BALB/C mice were intraperitoneally inoculated with CVB3 to induce myocarditis.From 24 h after infection,carvedilol was orally administered at a dose of 10 mg·kg-1·d-1 for 14 d continuously.Virus infection and normal controls were treated with same volume of PBS.Then,the myocardial histopathological changes,HW/BW ratio,serum TNF-α,mRNA expression of myocardial MMP-3 and TIMP-1 were determined.Results： Carvedilol significantly attenuated myocardial lesions and decreased HW/BW ratio.It also remarkably decreased serum TNF-α,down-regulated mRNA expression of MMP-3,and up-regulated mRNA expression of TIMP-1 as compared with myocarditis control.Conclusion： Carvedilol protects against CVB3-induced viral myocarditis in mice.Carvedilol exerts its beneficial effect by down-regulating MMP-3 mRNA expression and serum TNF-α,and up-regulating TIMP-1 mRNA expression.

关 键 词：卡维地洛 肿瘤坏死因子-α 基质金属蛋白酶-3 组织型基质金属蛋白酶抑制因子-1 病毒性心肌炎 

分 类 号：R972[医药卫生—药品]