摘要
目的研究清肠消澼饮对葡聚糖硫酸钠(DSS)诱导的小鼠溃疡性结肠炎模型的治疗作用。方法C57BL/6小鼠随机分为4组,每组10只,分别为正常组、模型组、清肠消澼饮组(14.71 g·kg^(-1)·d^(-1))和美沙拉秦组(1 g·kg^(-1)·d^(-1))。模型组和给药组自由饮用3%DSS连续7 d,建立溃疡性结肠炎小鼠模型,正常组给予正常饮用水。造模同时各组动物给予相应的药物灌肠,按照体质量10 mL·kg^(-1)剂量给药,共给药10 d。每天观察记录小鼠一般情况、体质量、DAI评分;采用HE染色法观察结肠组织病理变化,并进行病理学评分;采用16S rDNA测序技术检测小鼠肠道菌群结构变化,采用靶向胆汁酸代谢组学检测小鼠粪便中胆汁酸分子含量的变化。结果清肠消澼饮能够缓解DSS诱导的溃疡性结肠炎小鼠体质量下降(P<0.01),DAI评分升高,脾脏系数降低,胸腺系数上升,缓解结肠长度缩短,结肠病理评分降低(P<0.05,P<0.01)。清肠消澼饮能够增加厚壁菌门相对丰度,降低拟杆菌门、变形菌门等细菌的相对丰度,增加鼠杆菌属、毛螺旋菌属NK4A136、瘤胃球菌属等细菌的相对丰度(P<0.05,P<0.01)。此外,清肠消澼饮能够降低小鼠粪便中β-MCA、胆酸(CA)、鹅去氧胆酸(CDCA)、Tβ-MCA的含量,增加ω-MCA、脱氧胆汁酸(DCA)和TDCA的含量(P<0.05,P<0.01)。最后,对结肠炎、肠道菌群与胆汁酸代谢进行相关性分析发现,鼠杆菌属、毛螺旋菌属NK4A136、瘤胃球菌与次级胆汁酸中DCA和石胆酸(LCA)呈显著正相关。结论清肠消澼饮通过调控肠道菌群结构变化,调节菌群介导的胆汁酸代谢紊乱,降低肠道炎症,从而发挥治疗DSS诱导的溃疡性结肠炎小鼠的作用。
Objective To study the therapeutic effect of Qingchang Xiaopi Decoction on ulcerative colitis(UC)induced by dextran sulfate sodium(DSS).Methods C57BL/6 mice were randomly divided into four groups:normal group,model group,Qingchang Xiaopi Decoction group(14.71 g·kg^(-1)·d^(-1))and mesalazine group(1 g·kg^(-1)·d^(-1)),with 10 mice in each group.The mice in the model group and the drug administration group freely drank 3%DSS for seven consecutive days,and then the UC mouse model was established.The normal group was given normal drinking water.At the same time,the model mice in each group were given the corresponding drug lavage according to the body mass of 10 mL·kg^(-1) dose for 10 consecutive days.The general condition,body mass and DAI score of mice were observed and recorded every day.HE staining method was used to observe the pathological changes of colon tissue,and pathological score was carried out.16S rDNA sequencing technology was used to detect the structural changes of intestinal flora in mice,and targeted bile acid metabolomics was used to detect the changes of bile acid content in mice feces.Results Qingchang Xiaopi Decoction could alleviate the decrease of body mass(P<0.01),increase of DAI score,decrease of spleen index,increase of thymus index,shortening of colon length and decrease of colon pathological score(P<0.05,P<0.01)in DSS-induced UC mice.Qingchang Xiaopi Decoction could increase the relative abundance of Firmicutes,reduce the relative abundance of Bacteroidetes and Proteobacteria,and increase the relative abundance of Muribaculaceae,Lachnospiraceae NK4A136,Ruminococcus(P<0.05,P<0.01).In addition,Qingchang Xiaopi Decoction could decrease the content ofβ-MCA,CA,CDCA,Tβ-MCA,and increase the content ofω-MCA,deoxycholic acid(DCA),and TDCA in feces of mice(P<0.05,P<0.01).Finally,the correlation analysis of colitis,intestinal flora and bile acid metabolism found that there was a significant positive correlation between Muribaculaceae,Lachnospiraceae NK4A136,Ruminococcus and DCA,lithocholic acid(LCA)in secondary bile acids.Conclusion Qingchang Xiaopi Decoction can regulate the disturbance of bile acid metabolism mediated by intestinal flora and reduce intestinal inflammation by regulating the structural changes of intestinal flora,so as to play a role in the treatment of DSS-induced UC mice.
作者
潘思敏
白晓辉
陈雪如
黎祖鸣
吴苑
陈剑坤
黄绍刚
卢月
李际强
冯艳
PAN Simin;BAI Xiaohui;CHEN Xueru;LI Zuming;WU Yuan;CHEN Jiankun;HUANG Shaogang;LU Yue;LI Jiqiang;FENG Yan(The Second Clinical Medical School,Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China;The Second Affiliated Hospital of Guangzhou University of Chinese Medicine(Guangdong Provincial Hospital of Chinese Medicine),Guangzhou 510120 Guangdong,China;The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2024年第12期1842-1850,共9页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
国家自然科学基金面上项目(82174318)
广州市科技计划市校(院)联合资助基础与应用基础研究项目(2023A03J0738)
广东省自然科学基金面上项目(2021A1515011498)。
关键词
清肠消澼饮
溃疡性结肠炎
肠道菌群
胆汁酸代谢
葡聚糖硫酸钠
小鼠
Qingchang Xiaopi Decoction
ulcerative colitis
intestinal flora
bile acid metabolism
dextran sulfate sodium
mice
作者简介
潘思敏,女,博士研究生,研究方向:中医药防治急症疾病。Email:sevenpanpan@163.com。;通信作者:冯艳,女,硕士,副主任医师,研究方向:中医药防治肛肠疾病。Email:gonggongshiyongyx@163.com。;通信作者:李际强,男,博士,主任医师,研究方向:中医药防治呼吸系统疾病。Email:lijiqiangjizhen@163.com。;卢月,女,博士,副研究员,研究方向:中医药防治免疫性疾病。Email:gzyluyue@126.com。
