五种大黄苷元四四结合在脑缺血模型大鼠体内的药代动力学研究  

Pharmacokinetics of Random Combination of Four Rour Rhubarb Anthraquinones in Five in Rats with Thrombotic Focal Cerebral Ischemia

作　　者：赵迪[1,2,3] 刘学芳 冯素香[1,2,3] 董浩然 Zhao Di;Liu Xuefang;Feng Suxiang;Dong Haoran(Henan University of Traditional Chinese Medicine;Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan&Education Ministry of P.R.China;Henan Key Laboratory of Chinese Medicine for Respiratory Disease,Zhengzhou 450046)

机构地区：[1]河南中医药大学 [2]呼吸疾病中医药防治省部共建协同创新中心 [3]河南中医药防治呼吸病重点实验室,郑州450046

出　　处：《中药药理与临床》2020年第4期114-119,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金资助项目(编号:81274179);河南中医药大学“科研苗圃工程”项目(编号:MP2015-25)。

摘　　要：目的:探索五种大黄苷元四四结合在脑缺血模型大鼠体内的药代动力学特征。方法:健康雄性SD大鼠复制脑缺血模型,随机分5组,将芦荟大黄素13.05 mg/kg、大黄酚39.45 mg/kg、大黄素34.65 mg/kg、大黄素甲醚26.4 mg/kg、大黄酸17.25 mg/kg五种药物四个结合成组(组1.大黄酚+大黄素+大黄素甲醚+大黄酸;组2.芦荟大黄素+大黄酚+大黄素+大黄酸;组3.芦荟大黄素+大黄素+大黄素甲醚+大黄酸;组4.芦荟大黄素+大黄酚+大黄素甲醚+大黄酸;组5.芦荟大黄素+大黄酚+大黄素+大黄素甲醚),灌胃给药,不同时间点采集血浆。采用UPLC-MS/MS法测定五种成份在大鼠血浆中的浓度,计算药代动力学参数并进行统计分析。结果:与其它组合比较,芦荟大黄素与大黄酚在第4组合中t1/2、Cmax、AUC0-t、MRT0-∞显著升高,而Cl/F明显降低(P<0.05);大黄酸在第2组中AUC0-t、MRT0-∞达最大值,V/F与Cl/F降至最小,而在第3组合时t1/2显著降低,Cl/F达最大值(P<0.05);大黄素与大黄素甲醚药代动力学特征类似,与其它组合比较,在第3组中Tmax、Cmax、AUC0-t显著升高达最大值,而Cl/F明显降低(P<0.05)。结论:同一成分在不同结合组药代动力学参数变化较大,不同组合可影响药物在大鼠体内的代谢过程,药物间存在相互作用。Objective: To investigate the pharmacokinetic characteristics of random combination of four Rhubarb Anthraquinones in five in Thrombotic Focal Cerebral Ischemia-Induced Rats. Methods:SD male rats were used to establish the cerebral ischemia model, and were randomly divided into five groups. Five rhubarb anthraquinones: Aloe-emodin(13.05 mg/kg), Chrysophanol(39.45 mg/kg), Emodin(34.65 mg/kg), Physcion(26.4 mg/kg) and Rhein(17.25 mg/kg)were used and combined, 4 compounds in each group: 1. Chrysophano + Emodin + Physcion + Rhein, 2. Aloe-emodin + Chrysophanol + Emodin + Rhein, 3. Aloe-emodin + Emodin + Physcion + Rhein, 4. Aloe-emodin + Chrysophanol + Physcion + Rhein, 5. Aloe-emodin + Chrysophanol + Emodin + Physcion. After orally administration, blood samples were collected. The concentrations of the 5 compounds in rat plasma were determined by HPLC-MS/MS. The pharmacokinetic parameters were calculated and analyzed. Results:Compare with the other groups, the t1/2、Cmax、AUC0-t、MRT0-∞ of Aloe-emodin and Chrysophanol in group 4 were significantly increased, while the Cl/F was significantly decreased(P<0.05). The AUC0-t、MRT0-∞ of Rhein was increased to max level in group 2,but V/F and Cl/F was reduced to the minimum. In group 3, The t1/2 of Rhein had the minimum value and the Cl/F was the highest(P<0.05). Emodin and Physcion showed the similar pharmacokinetic characters, their Tmax、Cmax and AUC0-t were significantly increased to the maximum level, while the Cl/F was decreased to the minimum(P<0.05). Conclusion: The pharmacokinetic parameters of the same component greatly change in different groups,and show significant difference in the metabolic process in the rat, which suggests interactions among drugs.

关 键 词：大黄蒽醌苷元 脑缺血 药代动力学 相互作用 增效减毒 

分 类 号：R285.5[医药卫生—中药学]