文献类型：期刊文献

中文题名：毛蕊花糖苷及其代谢产物在常氧及缺氧大鼠体内组织分布比较

英文题名：Comparison of distribution of verbascoside in normoxic and hypoxic rats

作者：李茂星[1,2,3];王维刚[1,2,3];李晓琳[1,2];王芃[1,2,3]

第一作者：李茂星

机构：[1]联勤保障部队第九四〇医院临床药学科,甘肃兰州730050;[2]甘肃省高原药学行业技术中心,甘肃兰州730050;[3]甘肃中医药大学药学院,甘肃兰州730000

第一机构：联勤保障部队第九四〇医院临床药学科,甘肃兰州730050

年份：2022

卷号：47

期号：16

起止页码：4480

中文期刊名：中国中药杂志

外文期刊名：China Journal of Chinese Materia Medica

收录：CSTPCD;;Scopus;北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；PubMed;

基金：甘肃省重点研发计划项目(20YF3FA035);940医院青年培育项目(2021yxky060);940医院应急医学科研项目(20yjky018);中央高校基本科研业务费专项(31920200010)。

语种：中文

中文关键词：毛蕊花糖苷;常氧;缺氧;组织分布;咖啡酸;HPLC

外文关键词：verbascoside;normoxic;hypoxic;tissue distribution;caffeic acid;HPLC

摘要：该研究建立高效液相色谱(high-performance liquid chromatography, HPLC)同时测定大鼠组织样品中毛蕊花糖苷(verbascoside, VB)及其主要代谢产物咖啡酸(caffeic acid, CA)的方法。采用低压低氧动物实验舱模拟高原环境,制备缺氧大鼠模型。灌胃给予常氧及缺氧大鼠300 mg·kgVB后,于30、60、90 min采集大鼠心、肝、脾、肺、肾、大脑、肌肉、大肠、小肠和胃等组织,并采用HPLC法检测各组织中VB及CA的浓度,比较VB及其代谢产物CA在常氧及缺氧大鼠体内组织分布的差异。结果显示,毛蕊花糖苷经灌胃给药后,在常氧及缺氧大鼠中均可快速吸收并分布至包括大脑在内的各个组织,表明VB可通过血脑屏障;VB在胃肠道均主要分布于小肠中,提示VB主要吸收部位为小肠;此外,在肌肉和肺中均分布较多,其他组织仅有少量分布。除大脑、心和肌肉外,其他各组织均检测到了代谢产物CA,其中小肠中咖啡酸含量最多,其次是胃、大肠和肾,在肝、脾和肺中有少量分布(<50 ng·mL),表明毛蕊花糖苷可能主要在胃肠道中代谢产生咖啡酸并吸收,可能经过肾脏排泄。相比常氧大鼠,VB在缺氧大鼠组织中体现为分布减少和减慢,但组织与血浆中药物浓度的比值有所升高,表明进入体循环的VB分布至组织的相对比例增加。从组织分布角度研究结果为毛蕊花糖苷用于抗缺氧治疗提供依据,为抗缺氧给药方案的制定提供参考。
This study established a high performance liquid chromatography(HPLC) method for the simultaneous determination of verbascoside(VB) and its main metabolite caffeic acid(CA) in rat tissue samples. A low-pressure low-oxygen animal experimental chamber was used to simulate the plateau environment for establishing the hypoxic rat model. After intragastric administration of 300 mg·kgVB, the normoxic and hypoxic rats were sacrificed for the collection of heart, liver, spleen, lung, kidney, brain, muscle, large intestine, small intestine, and stomach tissue samples at the time points of 30, 60, and 90 min. VB and CA concentrations in each tissue sample were measured by HPLC, and the distribution of VB and CA in normoxic and hypoxic rats was compared. The results showed that after intragastric administration, VB can be rapidly absorbed and distributed into various tissues including brain in both normoxic and hypoxic rats, indicating that VB can pass through the blood-brain barrier. In the gastrointestinal tract, VB was mainly distributed in small intestine, which suggested that the main absorption site of VB was small intestine. A large amount of VB was detected in muscle and lung, and only a small amount in other tissues. CA was detected in other tissues except brain, heart, and muscle. Small intestine had the most abundant CA, followed by stomach, large intestine, and kidney, and only a small amount of CA was detected in the liver, spleen, and lung(<50 ng·mL). The results indicated that VB may be mainly absorbed and metabolized in the gastrointestinal tract to produce CA and was possibly excreted through kidney. Compared with normoxic rats, hypoxic rats had reduced and slow distribution of VB and increased ratio of VB concentration in tissue to plasma, which implied that the relative proportion of VB from systemic circulation to tissues was increased in hypoxic rats. This study provides a basis for the application of VB in anti-hypoxia therapy and for the formulation of anti-hypoxia dosing regimens.