黄连解毒汤中指标性成分药动学与药效学相关性的初步研究

Preliminery Study on Correlation between Pharmacokinetics and Pharmacodynamics with Index Components of Huanglian Jiedu Decoction

目的:研究黄连解毒汤中指标性成分在火热证脑缺血损伤模型大鼠的时量关系与抗火热证脑缺血效应的相关性。方法:火热证电凝法建立局灶性脑缺血模型,给药组,假手术组。给药组大鼠复制火热证脑缺血模型成功后灌胃给予黄连解毒汤,按0.083,0.25,0.5,0.75,1,2,3,4,6,8,12,24 h时间点取血,测定各指标性成分在大鼠体内的药时变化,绘制药-时曲线;取模型组,给药组,假手术组0.083,0.25,0.5,1,2,3,4,6,8,12,24 h时间点的脑组织,测定脑组织中白细胞介素(IL-6),肿瘤坏死因子(TNF-α)的变化,绘制时-效曲线。结合药时曲线和时效曲线,评价黄连解毒汤指标性成分在黄连解毒汤治疗火热证脑缺血疾病中所发挥的作用。结果:黄连解毒汤指标性成分的药动学行为不同;药效实验表明3种指标性成分的起效时间不同,持续时间亦不相同;黄连解毒汤的抗火热证缺血性脑损伤作用与其指标性成分的血药浓度密切相关。结论:黄连解毒汤全方能发挥抗火热证缺血性脑损伤作用,其作用的强弱与方中主要指标性成分在体内的含量相关,且各主要指标性成分发挥效应的时效存在差异。其对火热证脑缺血的保护作用机制可能与其抗炎作用相关,与传统中医上认为的黄连解毒汤有清热解毒的功效相一致。

Objective：To study the time-quantity relationship of index components of Huanglian Jiedu（HLJD） and its connection with the effect in ischemic brain injury in rats with syndrome of fire-heat after oral of Huanglian Jiedu decoction.Method：By electrocoagulation established model of focal cerebral ischemia with syndrome of fire-heat,after treatment group were orally administered Huanglian Jiedu decoction,catch blood at different time are as followes,0.083,0.25,0.5,0.75,1,2,3,4,6,8,12,24 h,determination of index components in rats draw the time-quantity curve;Catched brains at the points mentioned above,determinated the changes of IL-6,TNF-α,and draw the time-effect curve.Combined with time-quantity curve and time-effect curve,evaluate the function of index components in Huanglian Jiedu decoction treat ischemic disease with Syndrome of fire-heat.Result：Pharmacokinetics of index components of HLJD are different,which have a effect on its pharmacodynamics.Geniposide made a marked effect at prophase times after administration,while baicalin and baicalein made a lasting effect.Conclusion：Huanglian Jiedu decoction to play anti-ischemic brain with syndrome of fire-heat injury,the function connected with index components relevant content in the body,different components producted various time bar.