普拉梭菌上清增强肝纤维化小鼠肠道屏障功能抑制肝脏炎症  

Faecalibacterium prausnitzii supernatant inhibits liver inflammationby enhancing intestinal barrier function in mice with liver fibrosis

作　　者：陈曦[1] 张艾煜 康桐 孔光耀 杨军[3] 赵阳[2] CHEN Xi;ZHANG Aiyu;KANG Tong;KONG Guangyao;YANG Jun;ZHAO Yang(Precision Medicine Research Institute,Xi’an Jiaotong University,Xi’an 710115;National&Local Joint Engineering Research Center of Biodiagnosis and Biotherapy,The Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004;Department of Pathology,The Second Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710004,China)

机构地区：[1]西安交通大学精准医疗研究院,陕西西安710115 [2]西安交通大学第二附属医院生物诊断治疗国家地方联合工程研究中心,陕西西安710004 [3]西安交通大学第二附属医院病理科,陕西西安710004

出　　处：《西安交通大学学报(医学版)》2025年第1期112-118,共7页Journal of Xi’an Jiaotong University(Medical Sciences)

基　　金：国家自然科学基金青年科学基金项目(No.82100635);西安交通大学医学“基础-临床”融合创新项目(No.YXJLRH2022095)。

摘　　要：目的 探讨普拉梭菌培养上清对小鼠肠道屏障功能和肝纤维化进展的影响。方法 24只雄性C57BL/6小鼠随机分为3组:正常对照组(Control)、肝纤维化模型组(Model)、模型小鼠+普拉梭菌上清组(Model+S)。Model组和Model+S组小鼠腹腔注射四氯化碳诱导肝纤维化,共持续10周。造模2周后,Model+S组用细菌上清灌胃处理8周。HE染色观察结肠和肝脏组织病理形态,过碘酸雪夫染色、ELISA和异硫氰酸荧光素-葡聚糖(FITC-Dextran)荧光探针检测肠屏障功能损伤,16S rDNA测序分析肠道菌群结构变化,天狼星红染色观察肝纤维化程度,qPCR和ELISA检测肠道屏障功能、肝纤维化和炎症相关因子的表达。结果 与Model组相比,Model+S组小鼠肠道损伤程度和促炎因子表达降低,多种肠道屏障功能相关基因的表达显著提高,外周血中FITC-Dextran和肝脏脂多糖浓度均显著降低(均P<0.05),肠道菌群结构得到改善。此外,与Model组相比,Model+S组小鼠的肝脏功能和肝纤维化程度无明显差异,但肝脏中炎性细胞浸润减少,Tlr4、Il-6、Tnf-α等促炎因子的表达以及IL-6浓度显著降低(均P<0.05)。结论 普拉梭菌上清可改善肝纤维化小鼠的肠道屏障功能和肠道菌群失调,减轻肝脏炎症,但不影响肝纤维化进展。Objective To investigate the effects of the culture supernatant of Faecalibacterium prausnitzii(F.prausnitzii)on intestinal barrier function and liver fibrosis progression in mice.Methods A total of 24 male C57BL/6 mice were randomly assigned to three groups:normal control group(Control),liver fibrosis model group(Model),and model mice+F.prausnitzii supernatant group(Model+S).Hepatic fibrosis was induced by intraperitoneal injection of carbon tetrachloride in both the Model group and the Model+S group over a period of 10 weeks.Following a 2-week modeling period,the mice in the Model+S group were subjected to an 8-week treatment with bacterial supernatant.The colon and liver were analyzed for pathological morphology using HE staining.Additionally,impairment of intestinal barrier function was assessed by periodic acid schiff staining,ELISA,and fluorescein isothiocyanate-dextran(FITC-Dextran)fluorescent probe.Changes in the gut microbiota structure were analyzed with 16S rDNA sequencing.The degree of liver fibrosis was assessed using sirius red staining,and the expression levels of markers associated with intestinal barrier function,liver fibrosis,and inflammation were measured using qPCR and ELISA.Results Compared with the Model group,the severity of intestinal damage and the expressions of pro-inflammatory factors in the Model+S group were decreased.Additionally,there was a significant increase in the expressions of multiple genes related to intestinal barrier function,as well as a decrease in the concentration of FITC-Dextran in peripheral blood and lipopolysaccharide in the liver(all P<0.05),and there was an improvement in the composition of the gut microbiota.Furthermore,while the liver function and extent of liver fibrosis in the Model+S group did not show any significant differences compared to the Model group,there was a noticeable decrease in the infiltration of inflammatory cells within the liver.Additionally,the expressions of pro-inflammatory factors such as Tlr4,Il-6 and Tnf-α,and the concentration of

关 键 词：普拉梭菌 肠道屏障功能 肝纤维化 肠道菌群 炎症 

分 类 号：R657.3[医药卫生—外科学]