南方医科大学学报2025，Vol.45Issue(6)：1240-1250,11.DOI:10.12122/j.issn.1673-4254.2025.06.13
大麻二酚经PERK-eIF2α-ATF4-CHOP通路减轻多重脑震荡大鼠的神经元内质网应激和凋亡
Cannabidiol inhibits neuronal endoplasmic reticulum stress and apoptosis in rats with multiple concussions by regulating the PERK-eIF2α-ATF4-CHOP pathway
摘要
Abstract
Objective To explore the effects of cannabidiol on endoplasmic reticulum stress and neuronal apoptosis in rats with multiple concussions(MCC).Methods SD rats were randomized into sham group,MCC group,1%tween20(TW)treatment group,and low-dose(10 mg/kg)and high-dose(40 mg/kg)cannabidiol treatment groups.In all but the sham group,MCC models were established using a metal pendulum percussion device,after which the rats received daily intraperitoneal injections of the corresponding agents for 2 weeks.The expressions of PERK,eIF2α,ATF4,CHOP,TRIB3,p-Akt and pro-caspase-3 in the brain tissue of the rats were detected with qRT-PCR,Western blotting and immunofluorescence staining.The core targets of cannabidiol in treatment of traumatic brain injury(TBI)were identified by network pharmacology analysis,and molecular docking was carried out to simulate the interaction of cannabidiol with the factors related to endoplasmic reticulum stress and apoptosis.Results Compared with the sham-operated rats,the rat models of MCC showed significantly increased mRNA expressions of PERK,eIF2α and CHOP and protein expressions of PERK,eIF2α,ATF4,CHOP,TRIB3,p-AKT and pro-caspase-3 in the cerebral cortex.CBD treatment,especially at the high dose,obviously increased the expression of p-Akt and lowered the expression levels of the other factors tested in the rat models.Network pharmacology analysis indicated interactions of the core targets of CBD with the factors related to endoplasmic reticulum stress and TBI,and molecular docking study showed a high binding energy of CBD with multiple factors pertaining to endoplasmic reticulum stress and apoptosis.Conclusion MCC induce endoplasmic reticulum stress and apoptosis in rat brain tissues,for which CBD,especially at a high dose,provides neuroprotective effects by inhibiting endoplasmic reticulum stress and cell apoptosis.关键词
多重脑震荡/大麻二酚/内质网应激/神经元凋亡/PERK通路Key words
multiple cerebral concussions/cannabidiol/endoplasmic reticulum stress/neuronal apoptosis/PERK signaling pathway引用本文复制引用
杨毓甲,杨丽芳,吴雅玲,段兆达,于春泽,吴春云,于建云,杨力..大麻二酚经PERK-eIF2α-ATF4-CHOP通路减轻多重脑震荡大鼠的神经元内质网应激和凋亡[J].南方医科大学学报,2025,45(6):1240-1250,11.基金项目
国家自然科学基金(81960223) （81960223）
云南省昆明医科大学联合专项(202301AY070001-163) （202301AY070001-163）
云南省教育厅科学研究基金研究生项目(2024Y206) Supported by National Natural Science Foundation of China(81960223). （2024Y206）
