甘草次酸对大鼠橙皮素血浆浓度及组织分布影响的研究

Study on the Effect of Glycyrrhetinic Acid on the Plasma Concentration and Tissue Distributions of Hesperetin in Rats

目的研究在大鼠体内甘草次酸对橙皮素血浆浓度及组织分布的影响。方法将72只SD大鼠,体质量150~210g,随机分成4组,即实验高浓度组与低浓度组,对照组的高浓度组与低浓度组。每组中又包括三个小组即3,4,4.4 h。高浓度实验组灌胃20 mg/kg橙皮素+50 mg/kg甘草次酸,低浓度实验组灌胃10 mg/kg橙皮素+50mg/kg甘草次酸。对照组只灌胃橙皮素,剂量与实验组相同。灌胃给药后分别于3 h、4 h和4.4 h用摘眼球取血法取血,接着大鼠被断头处死,取出组织。血浆在85℃水浴中,加盐酸水解120 min,然后以乙腈为萃取剂,超声波为辅助提取,组织匀浆液用乙腈提取,利用高效液相色谱测定血浆及组织中橙皮素的浓度。结果血浆和组织中橙皮素测定的线性范围分别是0.05~10μg/ml和0.05~5μg/g,检测限分别是血浆0.012μg/ml和肝、肾0.005 7μg/g,肺0.011μg/g。测定回收率在是91%~104%之间。结论大鼠口服橙皮素后在血浆未能检测到游离橙皮素;灌胃20 mg/kg橙皮素时,甘草次酸对其药代动力学有影响(P<0.05);灌胃后橙皮素在大鼠体内分布特征是肝>肾>肺。

Objective To study the influence of glycyrrhetinic acid on the plasma concentration and tissue distributions of hesp- cretin in rats. Methods 72 SD rats, weighing 150 - 210 g, half male and half female, were distributed randomly into 4 groups,in- cluding control group of high and low concentration, experimental group of high and low concentration. Then each group was divid- ed into three sub - groups, namely group of 3 h,4 h and 4.4 h, respectively. Experimental group of high and low coneentratior were administered by gavage for a dose of 20 mg/kg hesperetin mixed with 50 mg/kg glycyrrhetinie acid and 10 mg,/kg hesperetir mixed with 50 mg/kg gryeyrrhetinie acid, respectively. The control group was administered by gavage for the same dose of that of the experimental group except glycyrrhetinic acid. Plasma samples were collected by picking eyeballs 3 h ,4 h and 4.4 h after ad- ministration. The rats were decapitated and remove tissue samples. Plasma were hydrolyzed at 85℃ for 120 min with hydrochloric acid , Then they were extracted with acetonitrile. Tissues were homogenated and then extracted with acetonitrile. Concentration of. Hesperetin was determined by HPLC. Results Iinear range of detection was O. 05 - 101μg/mL and 0.05 ~ O. 5 i^g/g for plasma anc tissues, Recoveries were 91% ～104 % with detection limits being 0. O12 Ixg/mL for plasma,0. 0057 μg/g for liver and kidney anc 0.011 txg,/g for lung, respectively, Conclusion No free hesperetin was detected in rats＇plasma after administration of it, glycyrrhet- inic acid can affect the pharmacokinetics of hesperetin in plasma while rats were administrated with 20mg/kg of hesperetin,Tissudistribution of hesperetin was liver 〉 kidney 〉 lung.