大黄游离蒽醌在正常和重症急性胰腺炎犬体内吸收动力学比较研究

目的研究重症急性胰腺炎(severe acute pancreatitis,SAP)对大黄游离蒽醌吸收动力学参数的影响。方法选取11只健康Beagle犬随机分为正常组(6只)及SAP组(5只)。制备SAP动物模型,两组经手术建立门静脉取血通道,给予大黄游离蒽醌(20mg/kg)灌胃,采用高效液相色谱(high performance liq-uid chromatography,HPLC)法测定门静脉与股动脉血液血浆中5种大黄游离蒽醌(芦荟大黄素、大黄酸、大黄素、大黄酚及大黄素甲醚)浓度,应用MATLAB2007B软件计算吸收动力学参数,使用统计矩法获取药物吸收半衰期(t1/2ka)、吸收达峰时间(Tmax)、峰浓度(Cmax)、药时曲线下面积AUC(0-∞)及药物在肠血管隔室的平均滞留时间(mean residence time,MRT),计算相应药物从胃肠道转运进入血液的转运速率(ka)。结果两组门静脉、股动脉药物吸收成分种类相同。多数动物门静脉各时间点均检测到芦荟大黄素,均在定量范围之内;每只动物门静脉各时间点均检测到大黄酸,个别时间点低于定量限;部分动物门静脉各时间点检测到大黄素与大黄酚,多数高于定量限;仅在少数动物门静脉个别时间点检测到大黄素甲醚。两组股动脉多数时间点检测到大黄酸,但部分时间点大黄酸血药浓度结果低于定量限,仅少数时间点检测到较低浓度芦荟大黄素、大黄素与大黄酚,未检测到大黄素甲醚。SAP组45min股动脉大黄酸血药浓度及门静脉大黄酚Cmax高于正常组,差异有统计学意义(P<0.05);其余指标差异均无统计学意义。大黄酸AUC在正常组及SAP组动物分别占总游离蒽醌的59.32%和66.07%。结论 SAP对大黄游离蒽醌的吸收动力学参数无明显影响,肠道与肝脏可能对大黄游离蒽醌存在明显代谢或转化作用。

A Comparative Study on the Absorption Kinetics Parameters of Rhubarb Free Anthraquinones between Normal Dogs and Dogs with Severe Acute Pancreatitis

Objective To study the effects of severe acute pancreatitis(SAP) on absorption kinetic parameters of rhubarb free anthraquinones.Methods Eleven healthy Beagle dogs were randomly divided into the normal group(n=6) and the SAP group(n=5).The SAP animal model was prepared by surgery through portal vein blood channel building to collect blood from normal dogs and dogs with SAP.The free anthraquinones(20 mg/kg) was given by gastrogavage.The concentrations of five anthraquinones(aloe emodin,rhein,emodin,chrysophanol,and physcion) in the blood plasma of the portal vein and the femoral artery were determined using high performance liquid chromatography(HPLC).The kinetic parameters were calculated using MATLAB2007B Software.The half life(t1/2Ka),the absorption peak time(Tmax),the peak concentration(Cmax),the area under the curve,and the mean residence time(MRT) were calculated using the statistical moment method.The transport velocity of corresponding medicines from the gastrointestinal tract to the blood(ka) was calculated.Results There was no difference in the chemical composition absorption type of the portal vein and the femory artery beween the two groups.Aloe emodin could be detected in the portal vein of each animal at each time point,and they were in the quantitative range.Rhein could be detected in the portal vein of each animal at each time point,and they were lower than the quantitative limit at few time points.Emodin and chrysophanol could be detected in the portal vein of partial animals at each time point,and most of them were higher than the quantitative limit.Physcion could be detected only in the portal vein of less animals at few time points.Rhein could be detected in the femoral artery at most time points,but the rhein plasma concentration at most time points were lower than the quantitative limit.Lower concentration of aloe emodin,emodin,and chrysophanol could be detected in the femoral artery at only few time points.Physcion was not detected in the femoral artery.The rhein plasma concentration of the femoral artery and the chrysophanol Cmax of the portal vein at 45 min were higher in the SAP group than in the normal group with statistical difference(P<0.05).There was no statistical difference in the rest indices.The AUC of rhein in the two groups were 59.32% and 66.07% of the total free anthraquinones respectively.Conclusions SAP could not obviously affect the absorption kinetics parameters of rhubarb free anthraquinones.The intestinal tract and the liver might possibly play important roles in metabolizing or transforming rhubarb free anthraquinones.