中国实验动物学报2025,Vol.33Issue(12):1715-1726,12.DOI:10.3969/j.issn.1005-4847.2025.12.001
阿格拉宾通过抑制NLRP3炎症小体活化调控创伤性脑损伤小鼠神经炎症
Arglabin regulates neuroinflammation in mice with traumatic brain injury by inhibiting NLRP3 inflammasome activation
摘要
Abstract
Objective To explore the effects and mechanism of arglabin on neuroinflammation in mice with traumatic brain injury(TBI).Methods Adult male C57BL/6J mice were divided randomly into:sham operation(Sham),Sham+Arglabin,TBI and TBI+Arglabin groups.TBI was induced by controlled cortical impact.After successful modeling,mice received 5 μg/kg arglabin by intraperitoneal injection,once a day until the material was retrieved.Neurological function was evaluated 3 weeks after the operation.Hematoxylin-eosin(HE)and Nissl staining were performed 4 weeks after the operation.Relative protein expression levels of NLRP3,apoptosis-associated speck-like protein containing a caspase-recruitment domain(ASC),and Caspase-1 in brain tissues were detected by Western Blot 3 d after surgery,and relative mRNA levels of the inflammatory factors interleukin(IL)-1β,IL-18,IL-6,inducible nitric oxide synthase(iNOS),IL-4,and Arg1 were detected by RT-qPCR.M1 and M2 cells were observed 7 d after the operation.Results Compared with the findings in the Sham group,in TBI group mice,nerve function was reduced(P<0.0001),the brain-tissue damage area was significantly increased(P<0.01),and neurons were largely lost(P<0.01).Additionally,NLRP3,ASC,and Caspase-1 protein levels in brain tissue were significantly increased(P<0.05),the proinflammatory cytokines IL-1β,IL-18,IL-6,and iNOS were significantly increased(P<0.05),and the anti-inflammatory cytokines IL-4 and Arg1 were significantly decreased(P<0.01).Lastly,levels of M1 type cells were significantly increased(P<0.01).Compared with the findings in the TBI group,in the TBI+Arglabin group,nerve function was significantly improved(P<0.01),the brain tissue-damage area was significantly reduced(P<0.01),neuronal loss was significantly reduced(P<0.01),In addition,NLRP3,ASC,and Caspase-1 proteins in brain tissue were significantly reduced(P<0.05),the proinflammatory cytokines IL-1β,IL-18,IL-6,and iNOS were significantly reduced(P<0.05),the anti-inflammatory cytokines IL-4 and Arg1 were significantly increased(P<0.01),and M2 type cells were significantly increased(P<0.01).Conclusions Arglabin improves the local immune microenvironment by inhibiting NLRP3 inflammasome activation to alleviate neuroinflammation in mice with TBI.关键词
创伤性脑损伤/神经炎症/阿格拉宾/NLRP3炎症小体Key words
traumatic brain injury/neuroinflammatory/Arglabin/NLRP3 inflammasome分类
生物科学引用本文复制引用
方壹万,周诗雨,姬浩鑫,闫华筝,高建雄,李睦融,吕合作,周慧芳..阿格拉宾通过抑制NLRP3炎症小体活化调控创伤性脑损伤小鼠神经炎症[J].中国实验动物学报,2025,33(12):1715-1726,12.基金项目
国家自然科学基金(82072416),蚌埠医科大学第一附属医院高水平科技创新团队资助项目(BYYFY2022TD001),国家级大学生创新训练项目(202410367086). Funded by National Natural Science Foundation of China(82072416),High-Level Science and Technology Innovation Team Funded by the First Affiliated Hospital of Bengbu Medical University(BYYFY2022TD001),National College Student Innovation Training Project(202410367086). (82072416)