基于肠道菌群探究葛根芩连汤短期治疗抗生素相关性腹泻  

To study on the short-term treatment of antibiotic-associated diarrhea with Gegen Qin-lian Decoction based on intestinal flora

作　　者：苏钢 杨光勇 张庚鑫 田维毅 王文佳 王平 涂小华 何光志 SU Gang;YANG Guang-yong;ZHANG Geng-xin;TIAN Wei-yi;WANG Wen-jia;WANG Ping;TU Xiao-hua;HEGuang-zhi(School of Basic Medicine,Guizhou University of Traditional Chinese Medicine,Guiyang Guizhou 550025,China)

机构地区：[1]贵州中医药大学基础医学院,贵州贵阳550025

出　　处：《时珍国医国药》2023年第9期2049-2053,共5页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(82060796);贵州省科技科学技术基金(黔科合基础[2020]1Y392);2018年度学术新苗项目(黔科合平台人才[2018]5766号-16);贵州省教育厅创新群体重大研究项目(黔教合KY字[2016]036);贵州省科技创新人才团队(黔科合平台人才[2020]5010);贵州省发改委工程研究中心建设项目[黔发改高技(2020)896号]。

摘　　要：目的探究葛根芩连汤(Gegen Qinlian Decoction,GQ)短期治疗对抗生素相关性腹泻(antibiotic-associated diarrhe-a,AAD)大鼠肠道菌群的影响。方法将80只SD大鼠适应性喂养1周后,根据随机双盲法分为8组(n=10):对照组0、1(N0、N1)、模型组0、1(M0、M1)、益生菌组(阳性对照组,P)、葛根芩连汤高、中、低剂量组(GQ-H、GQ-M、GQ-L)。除对照组外,其余各组灌胃克林霉素(250 mg/kg)制备AAD模型,1次/天,连续7天。大鼠出现腹泻后,分别于0天、3天麻醉后处死SD大鼠,无菌取结肠内容物备用。将两次所得粪便样本提取DNA,进行16S rRNA测序分析。结果克林霉素对肠道菌群多样性具有负面影响,在门水平克林霉素增加变形菌门相对丰度,而在属水平,克林霉素导致6个菌属相对丰度降低,包括瘤胃球菌、布劳氏菌、拟杆菌等。进一步代谢通路分析发现,克林霉素减少丁酸、乙酸等代谢通路;然而,经GQ治疗后,AAD大鼠肠道菌群结构明显改善,在门水平,GQ降低变形菌门相对丰度,在属水平,GQ增加梭菌和罕见小球菌相对丰度,并降低多种副杆状菌、颤螺菌相对丰度。在代谢通路方面,GQ增加硫胺素与精氨酸代谢通路。结论葛根芩连汤可能改善因长期服用克林霉素而引起的致病菌丰度增加及乙酸、丁酸代谢通路降低。Objective To study the effect of Gegen Qinlian Tang(GQ)on Gut Microbiota in Rats with Antibiotic-associated Di-arrhea(AAD).Methods After one week of adaptive feeding,80 SD rats were randomly divided into eight groups(n=10):the control group 0,1(N0,N1),the model group 0,1(M0,M1),the probiotic group(Positive control group,P),and the Gegen Qinlian Tang high,medium,and low dose groups(GQ-H,GQ-M,and GQ-L).Except for the control group,other groups were lavaged clindamycin(250 mg/kg)to prepare AAD,once daily for 7 days.After diarrhea,SD rats were sacrificed at 0d and 3d after anesthesia,then the colon contents were collected aseptically for standby..DNA was extracted from the feces samples ob-tained twice,at that time,16S rRNA sequencing was performed.Results Clindamycin harms the diversity of the gut microbiota.At the phylum level,clindamycin increases the relative abundance of Proteobacteria.In contrast,at the genus level,clindamycin leads to a decrease in the relative abundance of 6 genus,including Ruminococcus,Blautia,and Bacteroides.Further metabolic pathway analysis found that clindamycin reduces metabolic pathways such as butyric acid and acetic acid.However,after GQ treatment,the structure of the gut microbiota in AAD rats was significantly improved.At the phylum level,GQ reduces the rela-tive abundance of Proteobacteria.At the genus level,GQ increases the relative abundance of Clostridium and Subdoligranulum,and reduces the relative abundance of various Bacteroides and Spirochetes.In terms of metabolic pathways,GQ increases the met-abolic pathways of thiamine and arginine.Conclusion Gegen Qinlian Decoction could improve the phenomenon of increased a-bundance of pathogenic bacteria and decreased metabolism of acetic acid and butyric acid caused by long-term use of clindamy-cin.

关 键 词：葛根芩连汤 克林霉素 肠道菌群 短链脂肪酸 

分 类 号：R285.5[医药卫生—中药学]