药学学报, 2019, 54(1): 95-103
引用本文:
李瑶, 郭盛, 陶伟伟, 于金高, 宿树兰, 段金廒. 基于小鼠胃肠道系统毒性及利尿效应的大枣与巴豆霜配伍减毒机制研究[J]. 药学学报, 2019, 54(1): 95-103.
LI Yao, GUO Sheng, TAO Wei-wei, YU Jin-gao, SU Shu-lan, DUAN Jin-ao. Detoxification mechanism of Jujubae Fructus and Crotonis Semen Pulveratum based on the toxicity of gastrointestinal system and diuretic effect in mice[J]. Acta Pharmaceutica Sinica, 2019, 54(1): 95-103.

基于小鼠胃肠道系统毒性及利尿效应的大枣与巴豆霜配伍减毒机制研究
李瑶, 郭盛, 陶伟伟, 于金高, 宿树兰, 段金廒
南京中医药大学, 江苏省中药资源产业化过程协同创新中心/中药资源产业化与方剂创新药物国家地方联合工程研究中心/江苏省方剂高技术研究重点实验室, 江苏 南京 210023
摘要:
研究大枣对巴豆霜胃肠毒性及利尿效应的干预作用。将48只小鼠随机分为空白对照组(control)、巴豆霜低剂量组(0.039 g·kg-1·d-1,CTL)、巴豆霜高剂量组(0.078 g·kg-1·d-1,CTH)、大枣水提液组(9.75 g·kg-1·d-1,JF)、巴豆霜低剂量与大枣配伍组(巴豆霜0.039 g·kg-1·d-1,大枣9.75 g·kg-1·d-1,JFCTL)、巴豆霜高剂量与大枣配伍组(巴豆霜0.078 g·kg-1·d-1,大枣9.75 g·kg-1·d-1,JFCTH),每组8只。各组于给药第9天进行排尿量测定;给药10天后,收集新鲜粪便样品,采用16S rDNA测序的方法研究巴豆霜和大枣配伍前后肠道菌群的变化。所有实验方案均经南京中医药大学动物伦理委员会批准。结果表明,大枣与巴豆霜合用可减缓巴豆霜的快速利尿作用,显著上调单用巴豆霜后下降的血清白介素-2(IL-2)、白介素-6(IL-6)、胃泌素(GAS)和生长抑素(SS)水平,减轻巴豆霜导致的小鼠小肠组织损伤,并改善其引起的肠道菌群失调。大枣合用低剂量巴豆霜后可使SphingomonasOscillospira的相对丰度显著降低,大枣合用高剂量巴豆霜后致病菌属Bilophila水平降低。本研究表明大枣与巴豆霜配伍应用可在血清免疫指标、肠道运动、肠道损伤、肠道菌群结构等方面表现出一定的配伍减毒作用趋势。此外,大枣尚可减缓巴豆霜的逐水药势,呈现出一定的降效作用。
关键词:    大枣      巴豆霜      配伍减毒      肠道菌群      利尿效应     
Detoxification mechanism of Jujubae Fructus and Crotonis Semen Pulveratum based on the toxicity of gastrointestinal system and diuretic effect in mice
LI Yao, GUO Sheng, TAO Wei-wei, YU Jin-gao, SU Shu-lan, DUAN Jin-ao
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization/National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine/Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China
Abstract:
The aim of this study was to investigate the effect of Jujubae Fructus (JF) on the gastrointestinal toxicity and diuretic effect of Crotonis Semen Pulveratum (CT). Forty-eight mice were randomly divided into the control group, low dose of CT group (0.039 g·kg-1·d-1, CTL), high dose of CT group (0.078 g·kg-1·d-1, CTH), JF group (9.75 g·kg-1·d-1), low dose of CT combined with JF group (CT 0.039 g·kg-1·d-1 and JF 9.75 g·kg-1·d-1, JFCTL), high dose of CT combined with JF group (CT 0.078 g·kg-1·d-1 and JF 9.75 g·kg-1·d-1, JFCTH). On the 9th day of oral administration, the urine output of all mice was measured. After oral administration for ten days, fresh fecal samples were collected, and the 16S rDNA sequencing method was used to study the changes of intestinal bacteria when CT used alone and combined with JF. All experimental protocols were approved by the Animal Ethics Committee of Nanjing University of Chinese Medicine. The results showed that JF slowed down the rapid diuretic effect of CT, and significantly increased serum interleukin-2 (IL-2), interleukin-6 (IL-6), gastrin (GAS), somatostatin (SS). JF also reduced small intestine injury and improved the disorder of intestinal flora caused by CT. Low dose CT combined with JF significantly decreased the relative abundance of Sphingomonas and Oscillospira. The level of Bilophila was decreased after the combined application of high dose CT and JF. The results suggest that JF exhibited a tendency to reduce the toxicity of CT in the aspects of serum immune index, intestinal movement, intestinal damage, and intestinal microflora structure. In addition, the JF could also slow down the rapid diuretic effect of CT, behaving a tendency to reduce the clinical effect of CT.
Key words:    Jujubae Fructus    Crotonis Semen Pulveratum    detoxicity by compatibility    intestinal bacteria    diuretic effect   
收稿日期: 2018-07-16
DOI: 10.16438/j.0513-4870.2018-0647
基金项目: 国家自然科学基金资助项目(81473538);江苏省"六大人才高峰"资助项目(YY-026);教育部霍英东教育基金会高等院校青年教师基金项目(141040).
通讯作者: 郭盛,Tel/Fax:86-25-85811917,E-mail:guosheng@njucm.edu.cn;段金廒,E-mail:dja@njucm.edu.cn
Email: guosheng@njucm.edu.cn;dja@njucm.edu.cn
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