高脂血症大鼠灌胃黄连解毒汤后黄芩苷的药代动力学研究

Pharmacokinetics of baicalin in rats with hyperlipidemia after the intragastric administration of Huanglian Jiedu decoction

目的研究高脂血症大鼠灌胃黄连解毒汤提取物后,其成分黄芩苷的药代动力学特征,并探讨其药代动力学改变的机制。方法采用高脂饲料法诱导高脂血症大鼠模型,灌胃给予黄连解毒汤提取物、黄芩提取物,研究其主要成分黄芩苷的药代动力学特征。采用静脉注射黄芩苷研究其在高脂血症大鼠中的系统消除。制备肝微粒体,研究黄芩苷与微粒体温孵代谢转化情况。结果高脂血症大鼠灌胃黄连解毒汤提取物后黄芩苷的药代动力学参数发生显著改变,AUC显著增大,MRT显著延长(P<0.01)。灌胃给予黄芩提取物后,黄芩苷的药代动力学特征与灌胃黄连解毒汤后黄芩苷的药代动力学特征相似。静脉注射黄芩苷后,黄芩苷在高脂血症大鼠中的系统消除显著减慢,清除率显著降低(P<0.01)。黄芩苷与高脂血症大鼠肝微粒体温孵,其代谢转化相比正常大鼠肝微粒体温孵减慢。结论高脂血症大鼠灌胃黄连解毒汤提取物后黄芩苷的药代动力学发生改变,至少部分是由于高脂血症病理状态下肝脏的药物代谢转化能力降低,导致其AUC显著增加,MRT显著延长,提示临床使用黄连解毒汤治疗高脂血症时可能要调整剂量。

Objective To determine the pharmacokinetic characteristics of baicalin in rats with hyperlipidemia after the intragastric administration of the extract of Huanglian Jiedu decoction,and to explore the mechanism of the pharmacokinetic changes of baicalin.Methods Hyperlipidemia rat model was induced by high-fat diet.The extracts of Huanglian Jiedu decoction and Radix Scutellariae were given by gavage to determine the pharmacokinetics of baicalin.The systemic elimination of baicalin in rats with hyperlipidemia was studied by intravenous injection of baicalin.Liver microsomes were prepared to study the metabolization and transformation of baicalin when incubated with liver microsomes.Results After the intragastric administration of Huanglian Jiedu decoction extract,the pharmacokinetics of baicalin in rats with hyperlipidemia were remarkably changed,the AUC (area under the curve) of baicalin was significantly increased,and the MRT (mean residence time) of baicalin was significantly prolonged (P<0.01).After the intragastric administration of the baicalin extract,the pharmacokinetic characteristics of baicalin were similar to those of baicalin after the intragastric administration of Huanglian Jiedu decoction.After the intravenous administration of baicalin,the systemic elimination of baicalin in rats with hyperlipidemia was significantly slowed down,and the clearance rate of baicalin was significantly reduced (P<0.01).When baicalin was incubated with liver microsomes of hyperlipidemia rats,its metabolic transformation was slower than that when incubated with the liver microsomes of normal rats.Conclusion The pharmacokinetic changes of baicalin in rats with hyperlipidemia after the intragastric administration of Huanglian Jiedu decoction,at least in part,is due to the decrease of the ability of drug metabolism and transformation in the liver under the pathological state of hyperlipidemia,which may lead to significant increase in AUC of baicalin and significant extension of MRT of baicalin,suggesting that the dosage of Huanglian Jiedu decoction may be adjusted in the treatment of hyperlipidemia.