摘要
研究黄芩素(baicalein, Bai)对化疗性肠黏膜炎(chemotherapy-induced intestinal mucositis, CIM)小鼠的治疗作用及对肠道菌群的调节作用,探讨黄芩素对CIM的治疗作用与肠道菌群调控的关系。选取雄性Balb/c小鼠随机分为正常对照组、模型组和黄芩素给药组,联合5-氟尿嘧啶(5-fluorouracil, 5-FU)及伊利替康(irinotecan, IRI)制备CIM小鼠模型。动物福利和实验过程均遵循中国医学科学院药物研究所动物伦理委员会的规定。研究发现:黄芩素可显著抑制CIM小鼠体重下降、降低疾病活动指数及血清中白介素6 (interleukin 6, IL-6)和肿瘤坏死因子α(tumor necrosis factorα, TNF-α)含量。菌群多样性分析和物种差异分析显示,模型组小鼠肠道菌群组成与对照组存在明显差异,黄芩素对CIM小鼠粪便菌群具有调节作用,可降低拟杆菌属、大肠杆菌属、志贺氏菌属、副杆菌属、肠球菌属、梭状芽孢杆菌属和乳球菌属丰度,而显著升高穆氏杆菌属丰度。关联性分析显示, CIM小鼠血清的IL-6和TNF-α含量与梭状芽孢杆菌属、乳球菌属、拟杆菌属等丰度相关性显著。本研究表明黄芩素可有效改善小鼠化疗性肠黏膜炎,这一作用与其对肠道菌群的调节密切相关。
We evaluate the therapeutic effects of baicalein on chemotherapy-induced intestinal mucositis(CIM)in mice.The role of gut microflora regulation in the therapeutic effects of baicalein was investigated meanwhile.Male Balb/c mice were randomly divided into three groups including normal control group,model group and experimental group.Except for normal control group,mice were injected with 5-fluorouracil and irinotecan to induce CIM.Animal welfare and experimental procedures comply follow the rules of the Animal Ethics Committee of the Institute of Materia Medica,Chinese Academy of Medical Sciences.Baicalein significantly reduced disease activity index(DAI)of CIM mice and decreased the content of interleukin 6(IL-6)and tumor necrosis factor α(TNF-α)in serum.There were significant differences in the composition of the gut microbiota among groups according to the analysis ofαdiversity,β diversity,and the species differences.Compared with the normal control group,the Ruminococcaceae_UCG_014 and unclassified_f_Lachnospiraceae in mice of model group were significantly decreased while Bacteroides,Escherichia_Shigella,Enterococcus,Parabacteroides,Clostridium_sensu_stricto_1,and Lactococcus were significantly increased.Baicalein significantly decreased the abundance of Bacteroides,Escherichia_Shigella,Parabacteroides,Enterococcus,Clostridium_sensu_stricto_1,and Lactococcus.Meantime,norank_f_Muribaculaceae was notably increased by baicalein.The content of IL-6 and TNF-αin the serum of the three groups were positively correlated with the abundance of Clostridium_sensu_stricto_1,Lactococcus,Bacteroides,and Enterococcus according to correlation analysis.This study suggested the potential therapeutic effect of baicalein on CIM in mice.Regulation of gut microbiota probably plays a critical role in the therapeutic effects of baicalein.
作者
王睿
王霖
魏广义
刘楠楠
张莉
王淑美
杜冠华
WANG Rui;WANG Lin;WEI Guang-yi;LIU Nan-nan;ZHANG Li;WANG Shu-mei;DU Guan-hua(Guangdong Pharmaceutical University,Guangzhou 510006,China;Beijing Key Laboratory of Drug Target and Screening Research,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)
出处
《药学学报》
CAS
CSCD
北大核心
2020年第5期868-876,共9页
Acta Pharmaceutica Sinica
基金
国家重点研发计划资助项目(2018YFC0311005)
中国医学科学院医学与健康科技创新工程(2017-I2M-1-010)。
关键词
黄芩素
化疗性肠黏膜炎
肠道菌群
高通量测序
白介素6
肿瘤坏死因子α
baicalein
chemotherapy-induced intestinal mucositis
gut microbiota
high-throughput sequencing
interleukin 6
tumor necrosis factorα
作者简介
通讯作者:杜冠华,Tel/Fax:86-10-63165184,E-mail:dugh@imm.ac.cn。
