中风与神经疾病杂志2023，Vol.40Issue(12)：1096-1100,5.DOI:10.19845/j.cnki.zfysjjbzz.2023.0236
肠道菌群代谢产物TMAO激活HMGB1/NLRP3炎症通路促进小鼠脑缺血半暗带损伤的机制研究
Mechanism of gut microbiota metabolite TMAO activating inflammatory pathway HMGB1/NLRP3 to promote cerebral ischemic penumbra damage in mice
摘要
Abstract
Objective To explore the mechanism of the gut microbiota metabolite trimethylamine-N-oxide(TMAO)acting on high mobility group box 1(HMGB1)/NOD-like receptor protein 3(NLRP3)to regulate inflammatory response after cerebral ischemia/reperfusion(I/R)injury in mice.Methods A mouse atherosclerosis model was established by feeding on TMAO and high-fat diet.A mouse model of middle cerebral artery occlusion(MCAO)was prepared using the suture method.Mice were randomly divided into sham group,2-week-TMAO-feeding group,and 6-week-TMAO-feeding group.After I/R in-jury,we measured the protein levels of NLRP3,HMGB1,cleaved interleukin-1β(Cle-IL-1β),and zonula occludens-1(ZO-1)by Western blotting.After six weeks of TMAO feeding,mice were randomly divided into sham group,I/R group,TMAO+I/R group,and TMAO+DMB+I/R group.For each group,we scored neurological function,determined NLRP3,HMGB1,Cle-IL-1β,and ZO-1 protein expression by Western blot,measured brain infarct volume with TTC staining,and measured the water content of brain tissue.Results Compared with those of the sham group,NLRP3,HMGB1,and Cle-IL-1β protein expres-sion increased significantly and ZO-1 decreased significantly with the length of TMAO feeding(all P<0.05).Compared with the I/R group,the TMAO+I/R group showed a significant decline in neurological scores,significantly increased NLRP3,HMGB1,and Cle-IL-1β expression,significantly decreased ZO-1 expression,a significant increase in brain infarct volume,and a significant decrease in the water content of brain tissue(all P<0.05).With DMB lowering TMAO,the TMAO+DMB+I/R group had significantly better neurological scores,significantly lower NLRP3,HMGB1,and Cle-IL-1β levels,a significantly increased ZO-1 level,and significantly reduced brain infarct volume and brain tissue water content,as compared with the TMAO+I/R group(all P<0.05).Conclusion The gut microbiota metabolite TMAO can upregulate HMGB1/NLRP3-medi-ated inflammatory response in mice with cerebral I/R injury,worsening the breakdown of the blood-brain barrier to exacerbate brain tissue damage.关键词
肠道菌群/氧化三甲胺/NOD样受体热蛋白结构域相关蛋白3/高迁移率族蛋白B1/脑缺血再灌注损伤Key words
Gut microbiota/Trimethylamine-N-oxide/NOD-like receptor protein 3/High mobility group box 1/Cerebral ischemia/reperfusion injury分类
医药卫生引用本文复制引用
杨梅芳,程萍,陈治任,陈巍巍,黄文娟,张侠,谢志远..肠道菌群代谢产物TMAO激活HMGB1/NLRP3炎症通路促进小鼠脑缺血半暗带损伤的机制研究[J].中风与神经疾病杂志,2023,40(12):1096-1100,5.基金项目
国家自然科学基金青年科研基金项目(81501138) （81501138）
安徽省级研究生学术创新项目(2022xscx127) （2022xscx127）
徐州市科技局项目(KC20108) （KC20108）
徐州市医学重点人才项目(XWRCHT20220054) （XWRCHT20220054）
