三参饮对病毒性心肌炎慢性期Rho/Rock信号通路的作用  

Intervention Effect of Sanshen Decoction on Rho /Rock Signal Transduction Pathway in Chronic Phase Viral Myocarditis Mice

作　　者：王保奇[1] 殷子杰[1] 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：《中国实验方剂学杂志》2014年第6期140-144,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：浙江省自然科学基金项目(Y207808);郑州市科技创新团队项目(121PCXTD520);河南中医学院博士科研基金项目(BSJJ2010-14;BSJJ2009-46)

摘　　要：目的:观察小分子G蛋白(Rho)及Rho相关激酶(Rho/Rock)信号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:将120只BALB/c小鼠于第1次ip含柯萨奇病毒(CVB3)50%组织细胞感染量(TCID501×10-5)的1∶2 000病毒稀释液0.2 mL/只后,分别在第14,28天再次ip相同剂量,60 d后存活小鼠为病毒性心肌炎(VMC)心肌纤维化模型。将存活小鼠随机分为模型组、卡托普利组、三参饮高、中、低剂量组。灌胃治疗45 d后,采用ELISA检测血清Ⅰ型前胶原(PⅠNP)、Ⅲ型前胶原(PⅢNP),采用半定量RT-PCR法检测Rock的基因表达;放免法检测血清血管紧张素Ⅱ(AngⅡ)。采用雄性BALB/c小鼠间断多次ip CVB3的方法,建立VMC心肌纤维化模型。将存活小鼠随机分为模型组、卡托普利组、三参饮高、中、低剂量组。其中三参饮治疗组按高、中、低剂量3,2,1 g·kg-1,卡托普利治疗组按45 mg·kg-1ig,模型对照组、正常对照组ig等量生理盐水,每日1次。治疗45 d后,ELISA检测血清PⅠNP,PⅢNP,半定量RT-PCR法检测Rock的基因表达;放免法检测血清AngⅡ。结果:与正常组相比,模型组小鼠心肌PⅠNP,PⅢNP合成明显增高,与正常组相比差异有统计学意义(P<0.05);与模型组比较三参饮能够明显减少血清PⅠNP,PⅢNP表达,差异有统计学意义(P<0.05);Rho/Rock信号通路在病毒性心肌炎慢性期中表达水平较正常组升高,而经三参饮治疗后表达水平降低,差异有统计学意义(P<0.05)。模型组AngⅡ的含量也有相同的变化趋势(P<0.05)。结论:在慢性病毒性心肌炎心肌纤维化过程中,Rho/Rock信号通路是AngⅡ刺激成纤维细胞(CFBs)增殖和胶原合成的胞内信号转导机制之一,三参饮可通过阻断其传导抑制心肌纤维化。Objective：To investigate the role of Rho/Rock signal transduction pathway in the myocardial fibrosis （MF） in chronic phase viral myocarditis mice,and to study the therapeutic mechanism of Sanshen decoction （SD）.Method：Hundred and twenty BALB/c rats were inoculated ip with diluted coxsackievirus B3 （CVB3） EMEM solution fortnightly interval to establish the model of viral myocarditis （VMC） with MF.The survival model mice were randomized into 5 groups：model group,captopril group,high-,middle-and low-dosage SD groups.All the ras were treated by infusing the stomach with the medicine.The therapeutic dose of SD groups was respectively 3,2,1 g ·kg-1,and the captopril group was 45 mg ·kg-1,the model group and normal group were given the equivalence saline by gavage.Then N-terminal procollagen Ⅰ propeptide （P Ⅰ NP） and N-terminal procollagen Ⅲ propeptide （P Ⅲ NP） were detected by the means of enzyme-linked immunosorbant assay （ELISA）,and the gene expression of Rock1 was detected by RT-PCR,and the content of angiotensin Ⅱ （Ang Ⅱ） in serum by radioimmunoassay.Result：SD could decrease P Ⅰ NPand P Ⅲ NP obviously （P ＜ 0.05）,compared with the normal group.The expression levels of Rho/Rock signal pathway were higher than normal group （P ＜0.05） in the chronic phase of VMC.The contents of Ang Ⅱ in serum in model group were higher than the normal group （P ＜ 0.05）.Conclusion：The activation of Rho/Rock signal transduction pathway is one of the mechanism of the CFBs proliferation and collagen synthesis stimulated by Ang Ⅱ in myocardial fibrosis of VMC.Sanshen decoction can inhibit the restrain myocardial fibrosis by blocking the signal pathway.

关 键 词：三参饮 心肌纤维化 信号转导通路 RHO ROCK 

分 类 号：R285.5[医药卫生—中药学]