Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice  

作　　者：Yujia Liu Xue Han Yan Su Yiming Zhou Minhui Xu Jiyan Xu Zhengliang Ma Xiaoping Gu Tianjiao Xia 

机构地区：[1]Department of Anesthesiology,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing,Jiangsu Province,China [2]Medical School,Nanjing University,Nanjing,Jiangsu Province,China [3]Jiangsu Key Laboratory of Molecular Medicine,Nanjing University,Nanjing,Jiangsu Province,China [4]State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University,Nanjing,Jiangsu Province,China [5]Department of Anesthesiology,Zhongshan Hospital,Fudan University,Shanghai,China

出　　处：《Neural Regeneration Research》2025年第9期2727-2736,共10页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG);the Key Talent Project for Strengthening Health during the 13^(th)Five-Year Plan Period,No.ZDRCA2016069(to XG);the National Key R&D Program of China,No.2018YFC2001901(to XG);Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。

摘　　要：Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intrape

关 键 词：Chil1 hippocampus learning and memory M2 microglia NEUROINFLAMMATION postoperative cognitive dysfunction(POCD) recombinant CHI3L1 

分 类 号：R619[医药卫生—外科学]