聚乙二醇化葛根素的药效学实验研究

目的:对聚乙二醇(PEG)化葛根素前药(mPEG5000-Pur)体内药效学进行初步评价,为开发新型无溶血不良反应的葛根素制剂奠定基础。方法:采用垂体后叶素诱导大鼠急性心肌缺血模型,观察mPEG5000-Pur对心肌的保护作用;采用氯仿诱导小鼠心律失常模型,观察mPEG5000-Pur抗心律失常的作用。结果:葛根素PEG化后增强了对大鼠缺血心肌的保护作用;并且PEG化也可增强葛根素的抗小鼠心律失常作用,但是药效不呈剂量依赖性。结论:葛根素经PEG化后仍然保持了抗心肌缺血和抗心律失常的作用,且药效均优于相应剂量葛根素注射液组,这可能与PEG化后对葛根素体内组织分布改善有关。

Study on Pharmacology of Pegylated Puerarin

Objective：The pharmeodynamics of mPEG5000-Pur was evaluated,which would pave the way for exploring a novel no -hemolytic Pur agent. Methods：The acute myocardial ischemia model was induced by intravenously injecting poste- rior pituitrin hormone to observe cardiovascular pharmacology of mPEG5000- Pur. Anti - arrhythmias effect of the prodrug mPEG5000-Pur was evaluated by the model of arrhythmias induced by CHCI3. Results ：Pur and mPEG5000-Put had protec- ted ischemie heart against myocardial damage. In addition, both Put and mPEG5000- Put showed significant protecting effect against ventricular arrhythmia in mice, which was not in a dose -dependent manner. However, comparing with Pur, mPEG~o0 - Pur was more effective against arrhythmia. Conclusion： Pegylated puerarin had stronger effects of anti - myocardi- al isehemia and anti - arrhythmia compared with Pur. This may be resulting from the changes of tissue distribution of Put by pegylation. Our work verified that mPEGs000 - Put would be a promising agent for cardiovascular disease treatment.