丁酸梭菌预处理对葡聚糖硫酸钠诱导的结肠炎小鼠肝脏损伤的影响  

Effects of Clostridium butyricum Pretreatment on Liver Injury in Mice with Dextran Sulphate Sodium⁃Induced Colitis

作　　者：宋园园 肖英平[1] 马灵燕 吴酬飞[2] 杨彩梅 吕文涛 陈渠 王剑峰[4] SONG Yuanyuan;XIAO Yingping;MA Lingyan;WU Choufei;YANG Caimei;LYU Wentao;CHEN Qu;WANG Jianfeng(State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products,Institute of Agro-Product Safety and Nutrition,Zhejiang Academy of Agricultural Sciences,Hangzhou 310021,China;College of Life Science,Huzhou University,Huzhou 313000,China;College of Animal Science and Technology,Zhejiang A&F University,Hangzhou 311300,China;Hangzhou Original Seed Farm,Hangzhou 311115,China)

机构地区：[1]浙江省农业科学院农产品质量安全与营养研究所,省部共建农产品质量安全危害因子与风险防控国家重点实验室,杭州310021 [2]湖州师范学院生命科学学院,湖州313000 [3]浙江农林大学动物科技学院,杭州311300 [4]杭州市原种场,杭州311115

出　　处：《动物营养学报》2023年第8期5384-5395,共12页CHINESE JOURNAL OF ANIMAL NUTRITION

基　　金：国家自然科学基金项目(31972999)。

摘　　要：本试验旨在研究丁酸梭菌对葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠肝脏损伤的保护作用,并探究其机制。将10只C57BL/6J雄性小鼠分为CB组和DSS组,每组5只,CB组小鼠连续21 d灌胃200μL丁酸梭菌悬液(108CFU/mL),DSS组小鼠则给予等量生理盐水,而后2组小鼠通过饮水给予3%DSS 7 d诱导小鼠结肠炎,恢复3 d后测定小鼠肝脏组织中炎症因子白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的含量,并分析肝脏组织中转录组的变化。结果显示:丁酸梭菌预处理可减少DSS诱导结肠炎小鼠的体重、结肠长度、肝脏和脾脏重量的变化,同时改变血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)的活性;经丁酸梭菌预处理的小鼠肝脏组织结构变化较小,肝脏组织中炎症因子IL-6、IL-1β和TNF-α的含量降低。转录组学分析显示2组间肝脏组织中有575个差异表达基因,这些基因涉及的KEGG信号通路主要包括胆固醇代谢、谷胱甘肽代谢、细胞色素P450代谢和初级胆汁酸生物合成代谢,大都与脂质代谢相关。差异表达基因相对表达水平与炎症因子含量的相关性分析发现,细胞色素P450家族7亚家族B成员1(CYP7B1)和血管生成素样蛋白-8(ANGPTL8)基因相对表达水平与IL-6、IL-1β含量呈负相关;腺苷A1受体(ADORA1)、氧固醇结合蛋白样5(OSBPL5)、脂蛋白4(PLIN4)和肉毒碱脂酰转移酶1B(CPT_(1)B)基因相对表达水平与IL-6、IL-1β和TNF-α含量呈正相关。与DSS组相比,丁酸梭菌预处理后CYP7B1和ANGPTL8基因在多个通路中上调表达,而ADORA1、OSBPL5、PLIN4和CPT_(1)B基因在多个通路中下调表达。综上可知,丁酸梭菌能够有效预防DSS诱导结肠炎小鼠的肝脏损伤,其机制可能是通过调节胆固醇代谢、甘油三酯稳态和初级胆汁酸生物合成代谢相关基因的表达,降低肝脏中的炎症反应。This experiment was conducted to investigate the protective effect and mechanism of Clostridium bu⁃tyricum on liver injury in mice with dextran sulphate sodium(DSS)⁃induced colitis.Ten male C57BL/6J mice were divided into the CB group and DSS group(n=5).Mice in the CB group were orally administered with 200μL Clostridium butyricum suspension(108 CFU/mL)for 21 consecutive days as a pretreatment,while mice in the DSS group were given an equal amount of normal saline,and then 3%DSS was given by drinking water for 7 d to induce colitis in mice,and the contents of inflammatory factors interleukin⁃6(IL⁃6),interleu⁃kin⁃1β(IL⁃1β)and tumor necrosis factor⁃α(TNF⁃α)in mice liver tissue were determined for 3 d of recover⁃y,and liver tissue was analyzed for transcriptome changes.The results showed as follows:Clostridium butyri⁃cum pretreatment reduced the changes in body weight,colon length,liver and spleen weight induced by DSS in mice with colitis,and changed the activities of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum.The liver tissue structure of mice pretreated with Clostridium butyricum was less affected,and the contents of inflammatory factors IL⁃6,IL⁃1βand TNF⁃αwere lower.Transcriptome analysis showed 575 differentially expressed genes in the liver tissue between the two groups.The KEGG signaling pathways in⁃volved in these genes mainly included cholesterol metabolism,glutathione metabolism,cytochrome P450 me⁃tabolism,and primary bile acid biosynthesis,mostly related to lipid metabolism.Correlation analysis between differentially expressed gene relative expression levels and inflammatory factor contents showed that the relative expression levels of cytochrome P450 family 7 subfamily B member 1(CYP7B1)and angiopoietin⁃like 8(ANGPTL8)genes were negatively correlated with IL⁃6 and IL⁃1βcontents,while the relative expression lev⁃els of adenosine A1 receptor(ADORA1),oxysterol binding protein like 5(OSBPL5),perilipin 4(PLIN4)and carnitine palmitoy

关 键 词：丁酸梭菌 小鼠 葡聚糖硫酸钠 结肠炎 肝脏损伤 

分 类 号：Q939.9[生物学—微生物学]