黄连解毒汤的组合树脂精制物在脑缺血模型大鼠体内的整合药动学研究

Study on Integrated Pharmacokinetics of Huanglian Jiedu Tang Active Fraction Purified by Macroporous Resin in MCAO Rats

目的:研究黄连解毒汤有效部位(Huanglian Jiedu Tang active fraction,HLJDTAF)在脑缺血模型大鼠体内的整合药动学。方法:采用电凝法阻断大鼠大脑中动脉(MCA),建立脑缺血模型(MCAO),假手术组及模型组灌胃给予黄连解毒汤有效部位(HLJDTAF)后按不同时间点采血,用高效液相色谱法测定小檗碱、巴马汀、黄芩苷、栀子苷在大鼠体内的血药浓度,绘制药-时曲线,建立整合药动学模型。比较单一成分的药动学参数与整合药动学参数的差异。结果:假手术组血浆药物浓度-时间曲线下面积(AUC)(0-t),C max分别为(17.95±3.18)mg·L-1·h,(1.37±0.51)mg·L-1,平均驻留时间(MRT)(0-t),t1/2z分别为(11.19±0.59)h,(68.28±44.56)h;模型组AUC(0-t),C max分别为(18.65±1.00)mg·L-1·h,(1.61±0.12)mg·L-1,MRT(0-t);t1/2z分别为(9.61±0.39)h,(15.04±3.73)h。可知,相对于假手术组,模型组AUC(0-t),C max较高,MRT(0-t),t1/2z较小。说明黄连解毒汤有效部位在脑缺血模型大鼠体内吸收较好,达峰浓度更高;同时代谢加快,在体内停留时间较短。结论:黄连解毒汤有效部位(HLJDTAF)的整合药动学特征与单个成分的药动学特征基本一致。所获参数能够最大程度上表征中药复方多效应成分整体的体内处置规律,为建立中药复方药代动力学研究提供了一种研究方法。

Objective： To study the integrated pharmacokinetics of Huanglian Jiedu Tang active fraction（HLJDTAF） in middle cerebral artery occlusion（MCAO） rats. Method： MCAO model of rats was established by electrocoagulation,after oral administration with HLJDTAF,the blood samples in sham-operated and model group were collected at different time points. The plasma concentration of four component was determined;Combined with the time-concentration curve,the plasma concentration of components in sham-operated and model group was compared after oral administration. Result： Compared to the sham-operated group, area under the plasma concentration time curve（AUC）（0-t）, Cmaxof model group was higher and mean retention time（MRT）（0-t）, t1/2z was short. HLJDTAF hada better absorption and a higher peak concentration in MCAO rats;at the same time,HLJDTAF accelerated the metabolism and had a shorter residence time in the body. Conclusion： The integration pharmacokinetic characteristics are similar to pharmacokinetic characteristics of a single ingredient in HLJDTAF. The obtained parameters could express the whole characteristics of Chinese herbal compound.