清热养心颗粒中氧化苦参碱在病毒性心肌炎小鼠体内药动学-药效学相关性研究

Effect of Oxymatrine in Qingreyangxin Granules on Pharmacokinetics-pharmacodynamics Correlation in Viral Myocarditis Mice

目的:研究清热养心颗粒中氧化苦参碱在正常及病毒性心肌炎模型小鼠体内的药动学过程及其与药效作用的相关性。方法:以柯萨奇病毒B3(CVB3)诱导的病毒性心肌炎小鼠模型为研究对象,UHPLC-MS/MS检测小鼠血清中氧化苦参碱浓度,比较正常组和模型组小鼠体内药动学差异。同时,采用酶标仪测定各时间点血清中LDH、CK及IL-2活性,绘制药-效曲线。结果:与正常组相比,清热养心颗粒中氧化苦参碱在模型组小鼠血清中血药浓度高,消除速度慢,生物利用度高,血清中氧化苦参碱浓度与其抗病毒性心肌炎作用有关,能够降低LDH、CK水平,抑制IL-2的释放。结论:清热养心颗粒可减轻病毒性心肌炎导致的心肌损伤,其药效学与氧化苦参碱药动学具有一定的相关性。

Objective： To study the pharmacokinetics of oxymatrine in Qingreyangxin granules（QG） in normal mice and viral myocarditis mice and investigate its correlation with anti-viral myocarditis effect of QG. Methods： Models of viral myocarditis mice were produced by coxsackie B3 virus. An UHPLC-MS/MS method was applied to determine the concentration of oxymatrine in serum for comparing the difference in pharmacokinetics between normal rats and model rats after application of the same dose of QG. Meanwhile,a microplate reader was used to determine LDH, CK and IL-2 activities in serum at different time points for drawing dose-effect curves. Results： The results indicated that as compared with the normal group,oxymatrine in QG had higher serum concentrations, slower elimination rates and higher bioavailability in the model group. The oxymatrine concentrations in serum correlated with the anti-myocardial ischemia effects of QG, and inhibited the release of LDH, CK and IL-2. Conclusion： QG can alleviate myocardial injury induced by viral myocarditis, and the relationship between pharmacodynamics and oxymatrine concentrations meet the simple maximum effect PK-PD model.