基于宏基因组学探究葛根芩连汤改善抗生素相关性腹泻SD大鼠模型菌群失调的作用机制  

Macrogenomics-based study of the mechanism of GeGen QinLian Decoction in ameliorating dysbiosis in a rat model of antibiotic-associated diarrhea

作　　者：唐秋梅 韩雪 杨光勇 陈瑞 王文佳 涂小华 田维毅 蔡彦朋 陈驰 何光志 TANG Qiumei;HAN Xue;YANG Guangyong;CHEN Rui;WANG Wenjia;TU Xiaohua;TIAN Weiyi;CAI Yanpeng;CHEN Chi;HE Guangzhi(School of Basic Medicine,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;Dejiang County People’s Hospital,Dejiang 565200,China)

机构地区：[1]贵州中医药大学基础医学院,贵阳550025 [2]德江县人民医院,德江565200

出　　处：《中国实验动物学报》2024年第11期1379-1389,共11页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金项目(82060796);贵州省科技计划项目(黔科合支撑[2020]4Y187号);贵州省科技科学技术基金(黔科合基础[2020]1Y392);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,GQD)治疗抗生素相关性腹泻(antibiotic-associated diarrhoea,AAD)后大鼠肠道菌群以及功能的变化。方法将60只SPF级雌雄各半的SD大鼠喂养7 d后,按1∶5随机分为空白(Con)组和造模组。造模组大鼠使用克林霉素(250 mg/kg)灌胃造模,每天1次,连续7 d。造模成功后随机分为模型(Mod)组、葛根芩连汤高剂量(GQD-H)组、葛根芩连汤中剂量(GQD-M)组、葛根芩连汤低剂量(GQD-L)组、丽珠肠乐(LBP)组,每组10只。按给药剂量GQD-H组(10.08 g/kg)、GQD-M组(5.04 g/kg)、GQD-L组(2.52 g/kg)、LBP组(0.15 g/kg)灌胃干预,Con组和Mod组给予等体积生理盐水灌胃,每天1次,连续给药7 d后采集粪便,进行宏基因组学测序分析。结果α多样性和β多样性提示Mod组与GQD-H组、GQD-M组、GQD-L组之间肠道微生物多样性有差异;GQD各剂量组在门水平上增加厚壁菌门(Bacillota)的丰度,降低变形菌门(Pseudomonadota)丰度。在属水平上增加肠道黏液真杆菌属(Blautia)、拟杆菌属(Bacteroides)、Thomasclavelia、Mediterraneibacter相对丰度,降低Adlercreutzia、Muribaculum、Escherichia相对丰度;GQD上调氨基酸代谢途径、碳水化合物代谢途径、免疫疾病途径。结论GQD干预AAD后能改善肠道有益菌和致病菌的丰度比例,进而减轻肠道炎症反应,修复肠道免疫系统。Objective To investigate changes in the intestinal flora and function in rats with antibiotic-associated diarrhea(AAD)treated with GeGen QinLian Decoction(GQD).Methods Sixty male or female SPF-grade SD rats were fed for 7 days and then divided randomly into Control(Con)and modeling groups(1∶5 ratio).Rats in the modeling group received clindamycin 250 mg/kg by gavage once a day for 7 consecutive days.After successful modeling,the rats were divided randomly into model(Mod),high-dose GQD(GQD-H,10.08 g/kg),medium-dose GQD(GQD-M,5.04 g/kg),low-dose GQD(GQD-L,2.52 g/kg),and live Bifidobacterium power(LBP,0.15 g/kg)groups(n=10 rats per group).GQD and LBP were administered by gavage,and the Con and Mod groups were given an equal volume of saline by gavage once a day.Feces were collected after 7 consecutive days of administration for macrogenomics sequencing analysis.Resultsαdiversity andβdiversity suggested that intestinal microbial diversity differed between the Mod and GQD-treated groups.GQD increased the abundance of thick-walled bacteria and decreased the abundance of Aspergillus at the phylum level,and increased the relative abundances of the intestinal mucus bacteria Blautia,Bacteroides,Thomasclavelia,and Mediterraneibacter,and decreased the relative abundances of Adlercreutzia,Muribaculum,and Escherichia at the genus level.GQD also up-regulated the amino acid,carbohydrate,and immune disease pathways.Conclusions GQD improves the abundance ratio of beneficial and pathogenic intestinal bacteria in rats with antibiotic-associated diarrhea,which in turn reduces the intestinal inflammatory response and repairs the intestinal immune system.

关 键 词：葛根芩连汤 抗生素相关性腹泻 宏基因组学 肠道菌群 

分 类 号：Q95-33[生物学—动物学]