中国药理学通报2025，Vol.41Issue(7)：1346-1353,8.DOI:10.12360/CPB202411044
Ebselen抑制巨噬细胞过度炎性反应抗大肠杆菌急性感染
Inhibition of excessive inflammatory response of macrophages by Ebselen against acute Escherichia coli infection
摘要
Abstract
Aim To investigate the pharmacological mechanism of Ebselenin(Ebselen,EbSe)in the treat-ment of Escherichia coli(E.coli)infection,which had no significant inhibitory effect on Gram-negative bacte-ria,based on previous studies.Methods After EbSe intervention in E.coli infected Raw264.7 cells,the via-bility of Raw264.7 cells was determined by CCK-8 method,the morphology and structure of Raw264.7 cells were observed by electron microscope,and the in-tracellular bacterial load of Raw264.7 cells was calcu-lated by coated plate method.Polarization status of peritoneal macrophages,Raw264.7 intracellular NO and ROS content and intracellular HO-1 expression in Raw264.7 and E.coli acutely infected mice after E.co-li infection by flow cytometry.qPCR was used to detect the expression of related mRNAs in Raw264.7 cells.qPCR was used to detect the intracellular GSH content in Raw264.7 cells by spectrophotometric assay,and the state of cytoskeletal proteins was observed by immuno-fluorescence.Western blot assay was performed to de-tect the intracellular Txnrd1 expression level.Results Microtiter method,CCK-8,and electron microscopy observations showed that EbSe had no effect on the growth of E.coli and Raw264.7 cells in vitro.The re-sults of smear plate counting showed that EbSe reduced the intracellular bacterial load of Raw264.7 in the in-fected group.Flow cytometry results showed that EbSe upregulated the number of M2-type macrophages.The EbSe-treated infected group had reduced intracellular NO and ROS levels and increased GSH levels.The qPCR results showed that the expression of IL-6,IL-1β,and iNOS was decreased,and the expression of HO-1,Txnrd1,and Glut1 was increased in DHB4-in-fected Raw264.7 cells after EbSe treatment.Cytoskel-etal staining showed that the morphology of the EbSe-treated infected cells was similar to that of oxPAPC-in-duced cells.Western blot results showed the expres-sion of Txnrd1 protein in EbSe-treated infected cells in-creased.Conclusion EbSe exerts anti-E.coli acute infection effect by regulating macrophage polarization and inhibiting macrophage excessive inflammatory state.关键词
ebselen/大肠杆菌/抗菌/巨噬细胞/极化/急性感染Key words
ebselen/Escherichia coli/antibacterial/macrophages/polarization/acute infection引用本文复制引用
刘晓雯,邹黎黎,牟小琴,程创,龚双双,张浩然,贺靓,郑锡,王君,王栎清..Ebselen抑制巨噬细胞过度炎性反应抗大肠杆菌急性感染[J].中国药理学通报,2025,41(7):1346-1353,8.基金项目
国家自然科学基金资助项目(No 32170191) （No 32170191）
湖北省自然科学基金宜昌创新发展联合基金项目(No 2024AFD132,2024AFD144,2024AFD180) （No 2024AFD132,2024AFD144,2024AFD180）
湖北省老年胃肠癌精准防治临床医学中心开放基金(No 2022EGC-06,2022EGC-09) （No 2022EGC-06,2022EGC-09）
