基于离体外翻肠囊法研究滇白珠抗炎镇痛活性部位的肠吸收特性  

Intestinal absorption of anti-inflammatory and analgesic active fraction of Dianbaizhu with everted gut sac technique in vitro

作　　者：李晓 王秀环 赵怡程[1] 闫昕[1] 王乐 范书生 王小萍 许啸 何婷[1] 折改梅[1] Li Xiao;Wang Xiuhuan;Zhao Yicheng;Yan Xin;Wang Le;Fan Shusheng;Wang Xiaoping;Xu Xiao;He Ting;She Gaimei(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Intersection of Yangguang South Street and Baiyang East Road,Fangshan District,Beijing 102488,China)

机构地区：[1]北京中医药大学中药学院,北京102488

出　　处：《北京中医药大学学报》2020年第11期951-958,共8页Journal of Beijing University of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(No.81573692);北京中医药大学在读研究生项目(No.2019-JYB-XS-064);北京中医药大学大学生创新创业训练项目(No.201910026073,No.201910026397)。

摘　　要：目的考察滇白珠抗炎镇痛活性部位(ARF)的肠吸收特性。方法采用大鼠右后足足底注射完全弗氏佐剂方法建立佐剂诱导关节炎(AIA)动物模型,造模成功后将模型大鼠随机分为3组(ARF高、中、低浓度),每组3只,另取9只正常大鼠随机分为3组(ARF高、中、低浓度),每组3只;实验前12 h禁食不禁水,收集大鼠肠系的小肠部分10 cm左右,采用大鼠离体外翻肠囊法,考察滇白珠ARF高、中、低浓度给药后正常大鼠和AIA模型大鼠不同时间点的肠吸收差异。通过HPLC检测肠囊液样品中3个水杨酸甲酯糖苷类成分methyl benzoate-2-O-β-D-xylopyranosyl(1-2)[O-β-D-xylopyranosyl(1-6)]-O-β-D-glucopyranoside(MSTG-A)、methyl benzoate-2-O-β-D-glucopyranosyl(1-2)[O-β-D-xylopyranosyl(1-6)]-O-β-D-glucopyranoside(MSTG-B)及2-[(6-O-β-D-xylopyranosyl-β-D-glucopyranosyl)oxy]benzoic acid methyl ester(冬绿苷)的含量,计算累积吸收量,吸收速率常数及表观渗透系数,比较3个成分在正常大鼠及AIA模型大鼠的肠吸收情况。结果滇白珠ARF中的3个活性水杨酸甲酯糖苷类成分在正常大鼠及AIA模型大鼠中均为线性吸收(均r>0.9),符合零级吸收速率。各成分吸收速率常数与给药浓度及机体状态有关,在生理状态下,其吸收速率常数均随ARF浓度的增加而增加,说明3个指标成分属于被动扩散;而在病理状态下,其吸收速率常数均随浓度的增加先减小后增加。各成分在生理及病理状态下均吸收良好,表观渗透系数均大于1×10^(-6)cm/s,且在病理状态下吸收强于生理状态。结论滇白珠ARF中MSTG-A,MSTG-B和冬绿苷在正常及AIA模型大鼠离体小肠中的吸收均符合零级动力学过程,且病理状态对活性成分的吸收具有影响;选择外翻肠囊法可评价滇白珠ARF中3个水杨酸甲酯糖苷类成分的肠吸收特性。Objective To investigate the intestinal absorption characteristics of the anti-inflammatory and analgesic active fraction(ARF)of Dianbaizhu(Gaultheria yunnanensis,Gaultheria leucocarpa var.yunnanensis).Methods An adjuvant-induced arthritis(AIA)animal model was established by injecting complete Freund’s adjuvant into the sole of the right hind foot of the rat.After successful modeling the model rats were randomly divided into 3 groups(high,medium,and low concentration of ARF)(n=3 in each group),and another 9 normal rats were randomly divided into 3 groups(high,medium,and low concentration of ARF)(n=3 in each group).Rats in all groups were fasted for 12 hours before the experiment.About 10 cm of the small intestines of the rats were collected.Subsequently,the everted gut sac technique in vitro was used to investigate the difference in intestinal absorption between normal rats and AIA model rats after administration of low,medium and high concentrations of ARF at different times.The contents of three methyl salicylate glycosides in intestinal absorption samples,including methyl benzoate-2-O-β-D-xylopyranosyl(1-2)[O-β-D-xylopyranosyl(1-6)]-O-β-D-glucopyranoside(MSTG-A),methyl benzoate-2-O-β-D-glucopyranosyl(1-2)[O-β-D-xylopyranosyl(1-6)]-O-β-D-glucopyranoside(MSTG-B),and 2-[(6-O-β-D-xylopyranosyl-β-D-glucopyranosyl)oxy]benzoic acid methyl ester(Gaultherin),were detected by HPLC.The accumulative absorption,absorption rate constants,and apparent permeability coefficients were calculated to compare the components in the intestinal absorption fluid of normal rats and AIA model rats.Results The three methyl salicylate glycosides of ARF were all linearly absorbed in normal rats and AIA pathological models(r>0.9),which accorded with zero-order absorption rate.The absorption rate constant of each component was related to the concentration of drug and the state of the body.Physiologically,it increased with the increase of ARF concentration under physiological conditions,indicating that the three indicators belonged

关 键 词：滇白珠 水杨酸甲酯糖苷类成分 外翻肠囊模型 生理状态 病理状态 肠吸收特性 大鼠 

分 类 号：R284.1[医药卫生—中药学]