黄连解毒汤抗脑缺血有效部位中栀子苷的药动/药效学研究

Study on pharmacokinetics-pharmacodynamics of geniposide in HuanglianJieduTang active fraction(HLJDTAF)

目的:研究黄连解毒汤有效部位(HLJDTAF)中栀子苷在脑缺血模型大鼠的体内药动学行为与其药效学相关性。方法: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HLJDTAF后按不同时间点采血,测定栀子苷在大鼠体内的药-时变化绘制药-时曲线;测定含药血浆的超氧化物歧化酶(SOD)活力、丙二醛(MDA)含量绘制时-效曲线。结合药-时曲线及时-效曲线,比较给予相同剂量的HLJDTAF后栀子苷在假手术组及模型组中的血药浓度差异。结果:栀子苷在模型组大鼠体内吸收迅速,代谢快,维持的时间短,体现了在体内较强的循环性特点;与假手术组相比MCAO大鼠体内栀子苷吸收充分,血浆MDA含量明显升高,HLJDTAF能显著降低MCAO大鼠体内MDA的含量;与假手术组相比MCAO大鼠血浆SOD活性降低,HLJDTAF能升高MCAO大鼠血浆SOD活性。结论:HLJDTAF能发挥抗缺血性脑损伤作用,其作用的发挥与栀子苷在体内的含量有关;栀子苷抗缺血性脑损伤与SOD活性升高、MDA含量降低有关。

OBJECTIVE To study the pharmacokinetics pharmacodynamics of geniposide in HLJDTAF in MCAO model rats. METHODS MCAO model was established by electrocoagulation, shamoperated group and model group were given oral- ly with HLJDTAF, the rats bloods were collected at different time. The concentrations of geniposide in rats＂ plasma were de termined to draw the timeconcentration curve; the activity of SOD and the level of MDA in plasma were determined to draw the timeeffect curve. Combined with the timeconcentration curve and the timeeffect curve, the concentrations of geniposide in plasma of shamoperated group and model group were compared after oral administration of the same dose of HLJDTAF. RE SULTS Geniposide in model group was absorbed rapidly, fast metabolized and maintained shorter time, which reflected that in body with strong cyclical characteristics; compared with the shamoperated group, geniposide had a better absorption in MCAO rats and its content of MDA in plasma increased significantly. HLJDTAF could significantly reduce the content of MDA in MCAO rats;compared with shamoperated group, activity of SOD decreased in MCAO group and H LJDTAF could increase the activity of SOD. CONCLUSION HLJDTAF played a role in antiischemic brain injury, and its function connected with the content of geniposide in vivio ; geniposide had effect of antiischemic brain injury and could increase the activity of SOD and debase the content of MDA.