胆总管结扎诱导胆汁淤积性肝病促进肠道菌群的改变  

Cholestatic liver disease induced by bile duct ligation promotes changes of gut microbiota in mice

作　　者：杨博文 孙天宁 杨春燕 项红兵[2] 熊俊[4] 包仕廷 Yang Bowen;Sun Tianning;Yang Chunyan;Xiang Hongbing;Xiong Jun;Bao Shiting(Department of Hepatobiliary Surgery,Affiliated Hospital of Guangdong Medical University,Zhanjiang 524001,China;Department of Anesthesiology and Pain Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Surgical Laboratory of Clinical Skills Training Center of Guangdong Medical University,Zhanjiang 524001,China;Hepatobiliary Surgery Center,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430022,China)

机构地区：[1]广东医科大学附属医院肝胆外科,湛江524001 [2]华中科技大学同济医学院附属同济医院麻醉科,武汉430030 [3]广东医科大学临床技能培训中心外科实验室,湛江524001 [4]华中科技大学同济医学院附属协和医院肝胆外科,武汉430022

出　　处：《中华实验外科杂志》2022年第3期451-454,共4页Chinese Journal of Experimental Surgery

摘　　要：目的观察胆总管结扎诱导胆汁淤积性肝病对小鼠肠道菌群的影响。方法体重18~22 g雄性C57BL/6J小鼠16只,采用简单随机分组方法,随机分为假手术组(n=8)和胆汁淤积性肝病组(CLD组,n=8)。术后两周取材,通过血清肝功能酶和肝脏组织染色评价肝脏功能。采用16S rRNA基因测序检测小鼠肠道菌群。样本数据采用未配对t检验。结果与假手术组比较,胆汁淤积性肝病组小鼠血清肝功能酶高于假手术组[ALT:(889.9±485.1)U/L比(42.4±15.3)U/L,t=4.885,P<0.01;AST:(1044.0±588.0)U/L比(117.4±17.1)U/L,t=4.406,P<0.01;ALP:(1228.0±540.8)U/L比(171.2±24.8)U/L,t=5.464,P<0.01;TBIL:(59.17±12.28)μmol/L比(14.51±4.60)μmol/L,t=9.892,P<0.01],且肝脏出现显著病理改变;小鼠肠道菌群ɑ多样性高于假手术组(Chao1指数:1819.0±172.6比1498.0±170.8,t=4.388,P<0.01),肠道菌群组成发生明显改变,厚壁菌门/拟杆菌门比率高于假手术组(0.542±0.321比0.093±0.057,t=5.866,P<0.01),差异主要包括毛螺杆菌科(0.198±0.099比0.056±0.039,t=4.574,P<0.01),瘤胃球菌科(0.076±0.057比0.018±0.011,t=4.102,P<0.05),乳酸杆菌科(0.041±0.023比0.003±0.003,t=4.574,P<0.01),理研菌科(0.027±0.014比0.004±0.004,t=4.597,P<0.01)的富集。结论胆汁淤积性肝病导致肠道菌群出现特征性变化。Objective To investigate the effect of cholestatic liver disease(CLD)induced by bile duct ligation on gut microbiota in mice.Methods A total of 16 male C57BL/6J mice weighing 18-22 g were randomly divided into sham operation group(n=8)and CLD group(n=8).Liver function was evaluated by serum liver function enzyme and liver tissue staining.The gut microbiota of mice was detected by 16S rRNA gene sequencing technology.Results Compared with the control group,the results of serum liver function enzyme[alanine aminotransferase(ALT):(889.9±485.1)U/L vs.(42.4±15.3)U/L,t=4.885,P<0.01;aspartate aminotransferase(AST):(1044.0±588.0)U/L vs.(117.4±17.1)U/L,t=4.406,P<0.01;alkaline phosphatase(ALP):(1228.0±540.8)U/L vs.(171.2±24.8)U/L,t=5.464,P<0.01;total bilirubin(TBIL):(59.17±12.28)μmol/L vs.(14.51±4.60)μmol/L,t=9.892,P<0.01]and tissue staining in CLD group showed significant pathological changes in the liver.The composition of gut microbiota showed significantly changes.Theɑ-diversity(Chao1 index:1819.0±172.6 vs.1498.0±170.8,t=4.388,P<0.01)and ratio of Firmicutes/Bacteroides(0.542±0.321 vs.0.093±0.057,t=5.866,P<0.01)of gut microbiota significantly increased.The difference of gut microbiota was mainly manifested as an enrichment of Lachnospiraceae(0.198±0.099 vs.0.056±0.039,t=4.574,P<0.01),Ruminococcaceae(0.076±0.057 vs.0.018±0.011,t=4.102,P<0.05),Lactobacillaceae(0.041±0.023 vs.0.003±0.003,t=4.574,P<0.01)and Rikenellaceae(0.027±0.014 vs.0.004±0.004,t=4.597,P<0.01).Conclusion CLD causes characteristic changes of gut microbiota.

关 键 词：胆总管结扎 肠道菌群 胆汁淤积性肝病 

分 类 号：R575[医药卫生—消化系统]