急性酒精性肝损伤小鼠口服五味子总木脂素后8种木脂素的药代动力学分析  

Pharmacokinetic Analysis of 8 Lignans in Acute Alcoholic Liver Injury Mice after Oral Administration of Total Schisandra chinensis Lignans

作　　者：曾钦成 王阔 万久琛 宋兆芮 张志宏 王春梅[1] 李贺[1] 陈建光[1] 孙靖辉[1] ZENG Qincheng;WANG Kuo;WAN Jiuchen;SONG Zhaorui;ZHANG Zhihong;WANG Chunmei;LI He;CHEN Jianguang;SUN Jinghui(Pharmacy College of Beihua University,Jilin 132013,China)

机构地区：[1]北华大学药学院,吉林吉林132013

出　　处：《北华大学学报（自然科学版）》2024年第6期738-743,共6页Journal of Beihua University（Natural Science）

基　　金：国家自然科学基金面上项目(82274081)。

摘　　要：目的建立高效液相色谱法(HPLC),同时测定小鼠血浆中的8种五味子木脂素单体,分析正常小鼠和急性酒精性肝损伤小鼠灌胃五味子总木脂素后的药代动力学特征差异。方法选用雄性C57BL/6小鼠,一次性灌胃给予50%酒精溶液(12 mL/kg)建立急性酒精性肝损伤模型;于给药后不同时间点取血,测定小鼠血浆中的8种五味子木脂素单体,分析其药代动力学参数。结果在HPLC条件下,8种五味子木脂素的分离度良好;与正常组比较,急性酒精性肝损伤小鼠血液中8种五味子木脂素的半衰期(t_(1/2))明显增加,达峰时间(t_(max))延后,曲线下面积(AUC)、平均驻留时间(MRT)和表观分布容积(V_(d))也有所增加,清除率(CL)减少。结论急性酒精性肝损伤后,五味子木脂素在小鼠体内的暴露增加,半衰期体内作用时间延长,清除率减少,可能是酒精影响肠道吸收功能和肝药酶释放所导致的结果。Objective A high-performance liquid chromatography(HPLC)method was established for the sim-ultaneous determination of 8 Schisandra chinensis lignans in mouse plasma,and the pharmacokinetic characte-ristics of total Schisandr achinensis lignans in normal and acute alcoholic liver injury mice after gavage was analyzed.Method C57BL/6 male mice were selected and given a one-time gavage of 50%alcohol solution(12 mL/kg)to establish an acute alcoholic liver injury model.Blood was collected at different time points after administration.HPLC method was established for simultaneous dete rmination of 8 Schisandra chinensis lignans in mouse plasma,and their pharmacokinetic parameters were analyzed.Results Under the HPLC conditions of this study,8 Schisandra chinensis lignans were separated well.Compared with the normal group,the t_(1/2) of 8 lignans of mice with acute alcoholic liver injury significantly increased,and the t_(max) was delayed.The AUC,MRT and V_(d) also increased,and the CL decreased.Conclusion After acute alcoholic liver injury,the exposure of Schisandra chinensis lignans in mice increases,t 1/2 in vivo action time prolongs,and the elimination decreases.This may be the result of alcohol affecting intestinal absorption function and liver drug enzyme release.

关 键 词：五味子 木脂素 急性酒精性肝损伤 药代动力学 

分 类 号：R285.5[医药卫生—中药学]