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[正常犬与重症急性胰腺炎犬大黄游离蒽醌吸收动力学参数的比较研究]

[A comparative study on the absorption kinetics parameters of rhubarb free anthraquinones between normal dogs and dogs with severe acute pancreatitis].

作者信息

Yang Yong-Mao, Wang Ping, Zhang Yan

机构信息

Department of Pharmacology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137.

出版信息

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2012 Apr;32(4):494-8.

Abstract

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 (t(1/2Ka)), the absorption peak time (Tmax), the peak concentration (Cmax), the area under the curve [AUC(0-infinity)], 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 femoral artery between 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.

摘要

目的

研究重症急性胰腺炎(SAP)对大黄游离蒽醌吸收动力学参数的影响。

方法

11只健康比格犬随机分为正常组(n = 6)和SAP组(n = 5)。通过建立门静脉血道手术制备SAP动物模型,从正常犬和患SAP犬采集血液。经胃管给予游离蒽醌(20 mg/kg)。采用高效液相色谱法(HPLC)测定门静脉和股动脉血浆中5种蒽醌(芦荟大黄素、大黄酸、大黄素、 Chrysophanol和physcion)的浓度。使用MATLAB2007B软件计算动力学参数。采用统计矩法计算半衰期(t(1/2Ka))、吸收峰时间(Tmax)、峰浓度(Cmax)、曲线下面积[AUC(0 - infinity)]和平均驻留时间(MRT)。计算相应药物从胃肠道到血液的转运速度(ka)。

结果

两组门静脉和股动脉的化学成分吸收类型无差异。各时间点每只动物门静脉中均可检测到芦荟大黄素,且均在定量范围内。各时间点每只动物门静脉中均可检测到大黄酸,少数时间点低于定量限。各时间点部分动物门静脉中可检测到大黄素和Chrysophanol,多数高于定量限。仅在少数时间点较少动物的门静脉中可检测到physcion。多数时间点股动脉中可检测到大黄酸,但多数时间点大黄酸血浆浓度低于定量限。仅在少数时间点股动脉中可检测到较低浓度的芦荟大黄素、大黄素和Chrysophanol。股动脉中未检测到physcion。SAP组45 min时股动脉大黄酸血浆浓度和门静脉Chrysophanol Cmax高于正常组,差异有统计学意义(P<0.05)。其余指标无统计学差异。两组大黄酸的AUC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。肠道和肝脏可能在大黄游离蒽醌的代谢或转化中起重要作用。

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