三参饮对病毒性心肌炎慢性期TGFβ-Smad通路的干预研究  

Intervention Effect of Sanshen Decoction on TGFβ-Smad Signal Transduction Pathway in Chronic Phase Viral Myocarditis Mice

作　　者：王保奇[1] 殷子杰[1] 窦丽萍[2] 程志清[2] 

机构地区：[1]河南中医学院,郑州450008 [2]浙江中医药大学,杭州310053

出　　处：《中药新药与临床药理》2011年第2期144-148,共5页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：浙江省自然基金(Y207808);河南中医学院博士科研基金资助项目(BSJJ2009-46)

摘　　要：目的观察TGFβ-Smad传导通路在病毒性心肌炎慢性期心肌纤维化形成中的作用及三参饮治疗机制。方法 120只健康雄性Balb/c小鼠随机分组,其中30只采用间断多次腹腔注射柯萨奇病毒B3的方法,建立VMC心肌纤维化模型,另外10只注射不含病毒的Eagle'sMEM液作为正常对照组。两个月后模型制作成功。存活的小鼠随机随机分为5组,模型组、卡托普利组、三参饮高、中、低剂量组。分别给予卡托普利及不同浓度三参饮进行治疗,每日灌胃给药1次,45 d后结束。采用ELISA检测血清Ⅰ型、Ⅲ型胶原,采用半定量RT-PCR法检测转化生长因子(TGFβ1)的基因表达。免疫组化染色检测小鼠心肌Smad2/3,Smad7蛋白表达情况。结果感染CVB3后,ELISA检测模型组血清Ⅰ型、Ⅲ型胶原明显增高。TGFβ1表达水平较正常组升高,Smad2/3蛋白表达也升高,而smad7表达减少,与正常组相比差异均有统计学意义(P<0.05)。经过不同浓度三参饮及卡托普利治疗后,血清Ⅰ型、Ⅲ型胶原表达明显减少,TGFβ1、Smad2/3表达均有下降,而Smad7表达升高,差异均有统计学意义(P<0.05),与正常组相比差异有统计学意义(P<0.05)。结论阻断TGFβ-Smad通路可能是三参饮减少心肌组织Ⅰ、Ⅲ型胶原表达以抑制慢性病毒性心肌炎心肌纤维化的机制之一。Objective To investigate the role of TGFβ-Smad signal transduction pathway in the myocardial fibrosis（MF） in chronic phase viral myocarditis mice,and to study the therapeutic mechanism of Sanshen Decoction（SD）.Methods One hundred and twenty male Balb/c mice were randomly divided into groups.Of the 120 mice,30 mice were given incontinuous multiple intraperitoneal injection of diluted coxsackievirus B3（CVB3） to establish the model of viral myocarditis with MF,and 10 mice receiving intraperitoneal injection of EMEM solution without CVB3 served as the normal control.Two months later,the survival model mice were randomized into 5 groups： model group,captopril group,and high-,middle-and low-dosage SD groups.The rats were treated by captopril and different concentrations of SD every day,and the course of treatment was 45 days.We made pathological sections after the treatment,dyed the sections with Masson,and then observed the degree of MF.We detected the serum levels of collagen typeⅠand Ⅲ by the means of ELISA,examined the gene expression of tumor growth factor β1（TGFβ1） by RT-PCR,and detected the protein expression of myocardial Smad2/3 and Smad7 by immunohistochemistry.Results After being infected by CVB3,the model mice had higher serum levels of collagen typeⅠand Ⅲ,and higher TGFβ1 expression level and Smad2/3 protein expression level,but lower Smad7 protein expression level（P 0.05,compared with the normal group）.After treatment with SD and captopril,serum levels of collagen typeⅠand Ⅲ,TGFβ1 expression level and smad2/3 protein expression level were decreased,and smad7 protein level was increased（P 0.05,compared with the model group and the normal group）.Conclusion Blocking the TGFβ-Smad signal transduction pathway and reducing myocardial collagen typeⅠand Ⅲ expression may be one of the mechanisms of SD in inhibiting MF in viral myocarditis mice.

关 键 词：心肌纤维化 信号转导通路 转化生长因子Β1 

分 类 号：R285.5[医药卫生—中药学]