酸枣仁-五味子配伍对抗焦虑作用的影响及指标成分的肠吸收特性研究  

Effect of Ziziphi Spinosae Semen and Schisandrae Chinensis Fructus compatibility on anti-anxiety activty and intestinal absorption properties of effective components

作　　者：刘金凤 王晓玫 李佳园 杨雪[1] 魏晓嘉 王雨青 吕研 于佳禾 金重先 王春国[2] 石晋丽[1] LIU Jin-feng;WANG Xiao-mei;LI Jia-yuan;YANG Xue;WEI Xiao-jia;WANG Yu-qing;LYU Yan;YU Jia-he;JIN Zhong-xian;WANG Chun-guo;SHI Jin-li(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China;Research Institute of Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102488,China)

机构地区：[1]北京中医药大学中药学院,北京102488 [2]北京中医药大学中医药研究院,北京102488

出　　处：《中草药》2022年第16期5093-5106,共14页Chinese Traditional and Herbal Drugs

基　　金：国家“重大新药创制”科技重大专项(2012ZX09102-201-018)。

摘　　要：目的研究酸枣仁-五味子配伍前后的抗焦虑药效变化及指标成分斯皮诺素、五味子醇甲在焦虑模型大鼠小肠中的吸收特性变化。方法采用空瓶应激(empty bottle stress,EBS)和孤养结合束缚应激(restraint stress,RS)2种焦虑大鼠模型,通过旷场和高架十字迷宫实验评价酸枣仁-五味子配伍前后的抗焦虑药效;大鼠离体外翻肠囊实验和在体单向肠灌流实验结合HPLC法,测定配伍前后酸枣仁中斯皮诺素和五味子中五味子醇甲在焦虑模型大鼠十二指肠、空肠、回肠及整个小肠段的吸收情况。结果行为学实验表明酸枣仁、五味子均能减少焦虑模型大鼠的焦虑样行为,二者配伍后焦虑样行为的减少更为显著。在外翻肠囊实验中,五味子醇甲的吸收量比斯皮诺素约高1个数量级;配伍后斯皮诺素的吸收量下降,而五味子醇甲吸收量明显增加,表现在十二指肠、空肠和总吸收量的增加,并且其在空肠和回肠中的稳定性增加。在肠灌流实验中,给药30 min内,斯皮诺素基本完全吸收,但在酸枣仁单用时可能出现外排,配伍后外排减弱;给药1 h内,五味子醇甲基本完全吸收,未表现外排;配伍后斯皮诺素和五味子醇甲的吸收速率常数(Ka)和表观渗透系数(Papp)均保持较高水平。结论酸枣仁-五味子配伍后抗焦虑药效有所增强;配伍增加了斯皮诺素的溶出,减少了其外排,但降低了其吸收;配伍促进了五味子醇甲的吸收,增加了其在空肠和回肠的稳定性。从肠吸收屏障网络的角度揭示酸枣仁、五味子抗焦虑药效的发挥与其中的药效成分斯皮诺素、五味子醇甲在小肠保持良好的吸收密不可分,酸枣仁与五味子配伍后抗焦虑作用的增强可能与提高五味子醇甲在空肠和回肠的稳定性、增加五味子醇甲的吸收有关,这一结论为临床用药提供了科学依据。Objective To study the changes in anti-anxiety effects and the intestinal absorption properties of the key ingredients(spinosin and schisandrin)in two anxiety rat models,before and after the compatibility of Suanzaoren(Ziziphi Spinosae Semen,SZR)and Wuweizi(Schisandrae Chinensis Fructus,WWZ)herb pair.Methods Two anxiety rat models which were empty bottle stress(EBS)at the same time isolation and restraint stress(RS)combined with isolation were used to evaluate the anti-anxiety effect of before and after compatibility of SZR and WWZ by open field experiments and elevated cross maze experiments.The absorption of spinosin and schisandrin before and after compatibility of SZR and WWZ in duodenum,jejunum,ileum and the whole small intestine of anxiety model rats were determined by the in vitro everted gut sac experiment and in situ single-pass intestinal perfusion experiment combined with HPLC.Results The results of behavioral experiment showed that both SZR and WWZ could reduce the anxiety-like behavior of anxious rats,and the reduction of the anxiety-like behavior was more significant after the compatibility of the two.For the in vitro everted gut sac experiment,the absorption of schisandrin was about one order of magnitude higher than that of spinosin.After compatibility,the total absorption of spiniosin showed a downward trend,the absorption of schisandrin increased,which was manifested in the increase of duodenum,jejunum,and total absorption.Meanwhile,the schisandrin had good stability in jejunum and in ileum.For the in vivo single-pass intestinal perfusion experiment,the absorption of spinosin was fast and completed in 30 min of perfusion.The efflux may occur when SZR used alone.However,after compatibility,this efflux effect was weakened to a certain extent.Schisandrin was also absorbed quickly and completely within 1 h of perfusion,and no efflux effect was observed.And after compatibility,the absorption rate constant(Ka)and apparent permeability coefficient(Papp)of spinosin and schisandrin were both increased.Co

关 键 词：肠吸收 焦虑症 斯皮诺素 五味子醇甲 酸枣仁 五味子 配伍 

分 类 号：R285[医药卫生—中药学]