摘要
目的:探究大麻二酚(CBD)对创伤性脑损伤(TBI)大鼠氧化应激的保护作用及其与Nrf2-Keap1信号通路的关系。方法:成年雄性SD大鼠随机分为假手术组(Sham)、模型组(TBI+vehicle)、CBD干预组(TBI+CBD)、通路抑制剂组(TBI+CBD+ML385),采用改良Feeney自由落体法建立大鼠TBI模型,综合应用神经功能缺损(mNSS)评分、HE染色、免疫荧光染色、Western blot、RT-qPCR和ELISA技术观察大鼠脑组织病理变化、氧化应激及炎症反应情况。结果:模型组大鼠mNSS评分显著升高并出现神经细胞形态异常、炎症细胞浸润等病理改变,IL-1β和TNF-α阳性表达显著增强,GSH含量和Nrf2蛋白表达显著降低,ROS、MDA含量和Keap1 mRNA均显著升高。TBI+CBD组mNSS评分显著降低,脑组织病理情况改善,IL-1β、TNF-α阳性表达显著降低,GSH含量和Nrf2表达显著升高,且ROS、MDA含量和Keap1 mRNA水平均显著降低;ML385可明显抑制CBD的抗氧化作用。结论:CBD可通过Nrf2-Keap1通路抑制TBI后氧化应激,减轻TBI大鼠继发性病理损伤,发挥一定神经保护作用。
Objective:To investigate the protective effect of cannabidiol(CBD)against oxidative stress in rats with traumatic brain injury(TBI)and its relationship with Nrf2-Keap1 signaling pathway.Methods:Adult male SD rats were randomly divided into sham-operated group(Sham),model group(TBI+vehicle),CBD-intervention group(TBI+CBD)and pathway inhibitor group(TBI+CBD+ML385).Modified Feeney free-fall method was used to establish TBI model rats,pathological changes,oxidative stress and inflammation in rat brain tissue were observed by combination of neurological deficit scoring(mNSS),HE staining,immunofluores⁃cence staining,Western blot,RT-qPCR and ELISA.Results:mNSS score was significantly increased and pathological changes such as abnormal neuronal cell morphology and inflammatory cell infiltration were observed in model group,IL-1βand TNF-αpositive expressions were significantly enhanced,GSH content and Nrf2 protein expression were significantly reduced,ROS,MDA contents and Keap1 mRNA were significantly increased.mNSS score was significantly reduced in TBI+CBD group,pathological condition of brain tissue was improved,IL-1β,TNF-αpositive expressions were reduced,GSH content and Nrf2 expression were significantly increased,ROS,MDA contents and Keap1 mRNA were significantly decreased,and ML385 could significantly inhibit antioxidant effect of CBD.Conclusion:CBD can inhibit oxidative stress after TBI through Nrf2-Keap1 pathway,reduce secondary pathological injury in TBI rats,and play a certain neuroprotective role.
作者
朱娟
李恒希
李佳丽
凌腾晗
曹艳
尹爱平
马源
郭小兵
吴海鹰
李坪
ZHU Juan;LI Hengxi;LI Jiali;LING Tenghan;CAO Yan;YIN Aiping;MA Yuan;GUO Xiaobing;WU Haiying;LI Ping(Department of Human Anatomy&Embryology,School of Basic Medicine,Kunming Medical University,Kunming 650500,China;Department of Emergency and Intensive Care Unit,the First Affiliated Hospital of Kunming Medical University,Kunming 650032,China)
出处
《中国免疫学杂志》
北大核心
2025年第12期2824-2830,共7页
Chinese Journal of Immunology
基金
国家自然科学基金地区科学基金(82060241,82260387,82560263)
云南省基础研究计划项目-重点项目(202501AS070026)
云南省教育厅科学研究基金(2023J0217)
云南省科技厅科技计划基础研究专项(202301AS070020)
云南省科技厅昆明医科大学应用基础研究联合专项(202101AY070001-037)
国家大学生创新训练项目(202210678029)。
