黄芪-葛根配伍对葛根素在2型糖尿病大鼠体内药动学的影响  

Effect of puerarin pharmacokinetics on compatibility of Radix Astragali and Radix Puerariae in type Ⅱ diabetes mellitus rats

作　　者：袁丽君 涂星[1,2] 佟智斌 谭红 邱路雅 李莹 YUAN Lijun;TU xing;TONG Zhibin;TAN Hong;QIU Luya;LI Ying(Department of Traditional Chinese Medicine,Medical School,Hubei University for Nationalities,Enshi,Hubei 445000,China;Hubei Provincial Key Laboratory of Rheumatism Occurrence and Intervention,Enshi,Hubei 445000,China)

机构地区：[1]湖北民族学院医学院中医药系,湖北恩施445000 [2]风湿病发生与干预湖北省重点实验室,湖北恩施445000

出　　处：《重庆医学》2018年第31期3982-3986,共5页Chongqing medicine

基　　金：湖北省教育科学规划重点课题(2016GA024);湖北省重点实验室项目(OIR17005A)

摘　　要：目的探讨黄芪-葛根配伍对葛根素在2型糖尿病(T2MD)大鼠体内的药动学参数的影响。方法以腹腔注射低剂量链脲佐菌素(STZ)诱导T2MD模型大鼠为研究对象,灌胃给予黄芪-葛根2∶1和3∶1水煎液,于给药后不同时间点采集血浆样品,采用高效液相色谱法(HPLC)测定血浆样品中葛根素水平,绘制药-时曲线,进行房室模型拟合并计算药物动力学(PK)参数;以健康大鼠和T2MD大鼠同法给予黄芪-葛根0∶1水煎液作为对照。结果与健康大鼠比较,葛根素在T2MD大鼠体内吸收速率减缓(P<0.05)、消除时间和达峰时间延长(P<0.05),0~420min生物利用度(AUC_(0-420))、时间曲线下面积(AUMC)、平均滞留时间(MRT)均明显增加(P<0.05);表观分布容积(V/F)和表观清除率(CL/F)差异无统计学意义(P>0.05)。在T2MD大鼠中,与单用葛根比较,黄芪-葛根以2∶1和3∶1比例配伍时,葛根素体内吸收速率加快(P<0.05),而消除时间、V/F、CL/F、AUC_(0-420)、AUMC、MRT均明显增加(P<0.05);但达峰时间和峰浓度差异无统计学意义(P>0.05);且黄芪-葛根以3∶1比例配伍时上述指标变化更明显(P<0.05)。结论黄芪-葛根配伍协同增效作用可能与提高葛根素在体内的生物利用度,延长药物体内作用时间有关;且黄芪-葛根3∶1配伍效果更佳。Objective To investigate the effect of puerarin pharmacokinetics on compatibility of Radix Astragali and Radix Puerariae in typeⅡdiabetes mellitus(T2MD)rats,and provide references for clinical utilization.Methods T2MD rats induced by a single intraperitoneal injection of low dose streptozotocin(STZ)were chosen as the study objects,then given decoction of different compatibility of Radix Astragali and Radix Puerariae(2∶1 and 3∶1)by intragastric administration.Collected the plasma samples at different time points,used high performance liquid chromatography(HPLC)to detecte the level of puerarin,established the drug-time curve and the room model according to the data,then calculated the pharmacokinetics(PK)parameter;the compatibility of Radix Astragali and Radix Puerariae(0∶1)was administered as the control in the normal and T2MD rats.Results Compared with the normal rats,the absorption rate in the T2DM rats reduced significantly(P<0.05),while the eliminate time and the peak time increased(P<0.05),0-420 minutes bioavailability(AUC 0-420),area under concentration-time curve(AUMC)and mean retention time(MRT)increased significantly(P<0.05),there were no significant difference in the apparent volume of distribution(V/F)and clearance(CL/F).Compared with the compatibility of Radix Astragali and Radix Puerariae(0∶1)group,the eliminate time,V/F,CL/F,the absorption rate,AUC 0-420,AUMC and MRT increased significantly(P<0.05),while the peak time and the peak concentration showed no significant difference in the compatibility of Radix Astragali and Radix Puerariae(2∶1 and 3∶1)groups,these pharmacokinetics parameter changed more significantly in the compatibility of Radix Astragali and Radix Puerariae(3∶1)group(P<0.05).Conclusion The synergetic effects in pharmacological of compatibility of Radix Astragali and Radix Puerariae may be related to improving the bioavailability of puerarin and prolonging the action time of the drug,and the best compatibility of Radix Astragali and Radix Puerariae is 3∶1.

关 键 词：黄芪 葛根 糖尿病 2型 协同增效 药动学 高效液相色谱法 

分 类 号：R285.5[医药卫生—中药学]