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目的研究三七皂苷R_1在心肌缺血疾病大鼠模型体内的药动学与药效作用的规律。方法建立垂体后叶素致心肌缺血模型,静脉注射三七皂苷R_1(100 mg·kg~(-1))后采用HPLC测定各时间点的三七皂苷R_1浓度,计算药动学变化参数并测定血流动力学及抗氧化相关指标,利用药动学/药效学(PK/PD)结合模型研究三七皂苷R_1改善心肌缺血时效的关系。结果三七皂苷R_1能升高模型大鼠血清肌酸激酶、谷胱甘肽过氧化物酶及谷胱甘肽的含量,且能同时降低MDA的含量;与正常大鼠比较,模型大鼠体内的AUC_(0-t)和AUC_(0-∞)显著增加,平均驻留时间延长;PK/PD结合模型显示药物效应滞后于血药浓度。结论三七皂苷R_1的药物效应与效应室浓度相关性良好;该方法专属性强、灵敏度高,可用于研究三七皂苷R_1的作用效能、量效关系和维持时间。
Objective To study the pharmacokinetics and pharmacodynamics of notoginsenoside R_1 in a rat model of myocardial ischemia. Methods The model of posterior pituitary-induced myocardium ischemia was established. After intravenous injection of notoginsenoside R_1 (100 mg · kg -1), the concentration of notoginsenoside R_1 at each time point was determined by HPLC. The pharmacokinetic parameters were calculated and the blood Flow mechanics and anti-oxidation related indicators, the use of pharmacokinetics / pharmacodynamics (PK / PD) combined model of notoginsenoside R_1 to improve the relationship between myocardial ischemia. Results Notoginsenoside R_1 could increase the content of serum creatine kinase, glutathione peroxidase and glutathione in model rats and decrease the content of MDA at the same time. Compared with normal rats, The AUC_ (0-t) and AUC_ (0-∞) increased significantly and the average residence time prolonged. The PK / PD binding model showed that the drug effect lagged behind the plasma concentration. Conclusion The pharmacological effects of notoginsenoside R_1 have a good correlation with the concentration of effector compartment. The method is specific and sensitive and can be used to study the action potency, the dose-effect relationship and the maintenance time of notoginsenoside R_1.