大麻二酚对大鼠多重脑震荡炎症反应的抑制作用

杨丽芳, 于春泽, 张先俊, 吴春云, 于建云, 杨力

中国临床解剖学杂志 ›› 2024, Vol. 42 ›› Issue (3) : 278-283.

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中国临床解剖学杂志 ›› 2024, Vol. 42 ›› Issue (3) : 278-283. DOI: 10.13418/j.issn.1001-165x.2024.3.07
实验研究

大麻二酚对大鼠多重脑震荡炎症反应的抑制作用

  • 杨丽芳1#,    于春泽1,2#,    张先俊3,4,    吴春云1,    于建云3*,    杨力1*
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Inhibition effects of cannabidiol on inflammatory response following multiple cerebral concussions in rats

  • Yang Lifang1# ,Yu Chunze 1,2#,Zhang Xianjun 3,4,Wu Chunyun1, Yu Jianyun3*,Yang Li1*
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摘要

目的    探究大麻二酚(CBD)抑制大鼠多重脑震荡神经炎症、保护神经组织的机制。  方法    制备大鼠多重脑震荡模型(MCC),分别采用HE、免疫组化染色检测多重脑震荡后神经元和小胶质细胞的变化及大麻二酚的保护作用。应用Western blot检测不同脑区Iba-1(小胶质细胞标记物)及炎症因子IL-1β、TNFα的表达。  结果    HE染色显示,较之Sham组,大鼠MCC后神经元出现明显病理改变;CBD干预后神经元形态趋于正常,高剂量组更显著。免疫组化显示,与Sham组呈静息状态的小胶质细胞相比,MCC后数量增加呈激活状态,CBD干预后小胶质细胞向静息态恢复,高剂量组更明显。Western blot结果显示:大鼠MCC后Iba-1、IL-1β、TNFα蛋白表达显著升高(P<0.05);CBD干预可下调不同脑区Iba-1、IL-1β和TNFα的表达(P<0.05)。  结论    大麻二酚可减轻多重脑震荡大鼠皮质及海马的炎症反应,发挥神经保护作用。

Abstract

Objective   To investigate the mechanism by which cannabidiol (CBD) inhibits neuro-inflammation and protects neural tissue in a rat model of multiple cerebral concussions.    Methods  Rat models of multiple cerebral concussions (MCC) were established, and Hematoxylin-eosin(HE) and immunohistochemical staining were used to assess changes in neurons and microglial cells after multiple cerebral concussions and the protective effects of CBD. Western blot was performed to measure the expression of microglial cell marker Iba-1 and pro-inflammatory factors IL-1β and TNFα in different brain regions. Results    HE staining revealed significant pathological changes in neurons following MCC in rats compared to the Sham group. CBD intervention led to a restoration of normal neuronal morphology, with a more pronounced effect observed in the high-dose group. Immunohistochemical staining showed that microglial cells in the Sham group were in a resting state, while their numbers increased and exhibited an activated state after MCC. CBD intervention resulted in a shift of microglial cells towards a resting state, with a more significant effect observed in the high-dose group. Western blot demonstrated a significant upregulation of Iba-1, IL-1β, and TNFα protein levels in different brain regions after MCC (P<0.05). CBD intervention led to a downregulation of Iba-1, IL-1β, and TNFα expression in these brain regions (P<0.05).  Conclusions  Cannabidiol could alleviate inflammatory response in the cortex and hippocampus of rats with multiple cerebral concussions and exhibit neuroprotective effects.

关键词

大麻二酚;  /   / 多重脑震荡;  /   / 炎症

Key words

Cannabidiol;  /   / Multiple cerebral concussions;  /   / Inflammation

引用本文

导出引用
杨丽芳, 于春泽, 张先俊, 吴春云, 于建云, 杨力. 大麻二酚对大鼠多重脑震荡炎症反应的抑制作用[J]. 中国临床解剖学杂志. 2024, 42(3): 278-283 https://doi.org/10.13418/j.issn.1001-165x.2024.3.07
Yang Lifang, Yu Chunze, Zhang Xianjun, Wu Chunyun, Yu Jianyun, Yang Li. Inhibition effects of cannabidiol on inflammatory response following multiple cerebral concussions in rats[J]. Chinese Journal of Clinical Anatomy. 2024, 42(3): 278-283 https://doi.org/10.13418/j.issn.1001-165x.2024.3.07
中图分类号: R651.15         

参考文献

[1]  Koza LA, Pena C, Russell M, et al. Immunocal® limits gliosis in mouse models of repetitive mild-moderate traumatic brain injury[J]. Brain Res, 2023, 1808: 148338. DOI: 10.1016/j.brainres.2023.148338.
[2]  Mc Fie S, Abrahams S, Patricios J, Suter J, et al. Inflammatory and apoptotic signalling pathways and concussion severity: a genetic association study[J].J Sports Sci, 2018, 36(19): 2226-2234. DOI: 10.1080/02640414.2018.1448570.
[3] Guo H, Zheng L, Xu H, et al. Neurobiological Links between Stress, Brain Injury, and Disease[J]. Oxid Med Cell Longev, 2022, 2022: 8111022. DOI: 10.1155/2022/8111022.
[4] Sen T, Saha P, Gupta R, et al. Aberrant ER Stress Induced Neuronal-IFNβ Elicits White Matter Injury Due to Microglial Activation and T-Cell Infiltration after TBI[J]. J Neurosci, 2020, 40(2): 424-446. DOI: 10.1523/JNEUROSCI.0718-19.2019.
[5]  Nguyen T, Nguyen N, Cochran AG, et al. Repeated closed-head mild traumatic brain injury-induced inflammation is associated with nociceptive sensitization[J]. J Neuroinflammation, 2023, 20(1): 196. DOI: 10.1186/s12974-023-02871-1.
[6]  Wang L, Wu X, Yang G, et al. Cannabidiol alleviates the damage to dopaminergic neurons in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahy dropyridine-induced Parkinson's Disease mice via regulating neuronal apoptosis and neuroinflammation[J]. Neuroscience, 2022, 498: 64-72. DOI: 10.1016/j.neuroscience.2022.06.036.
[7] Castillo-Arellano J, Canseco-Alba A, Cutler SJ, León F. The polypharmacological effects of cannabidiol[J]. Molecules, 2023, 28(7): 3271. DOI: 10.3390/molecules28073271.
[8] Zhang H, Zhang Z, Wang Z, et al. Current evidence for pharmacological management of pediatric concussion: a systematic review[J]. Exp Ther Med, 2018, 16(3): 2295-2302. DOI: 10.3892/etm.2018.6474.
[9]  于建云,李娟娟, 韩晓华,等. 脑震荡鼠细胞组织病理学研究[J]. 昆明医学院学报, 2003, (2): 1-5.
[10] 杨雪珂, 张晓丽娜, 钟正, 等.天麻素通过Notch信号通路调控激活的BV2小胶质细胞的研究[J].中国临床解剖学杂志, 2023, 41(3): 318-323. DOI:10.13418/j.issn.1001-165x.2023.3.12.
[11]Poulose SM, Bielinski DF, Carey A, et al. Modulation of oxidative stress, inflammation, au-tophagy and expression of Nrf2 in hippocampus and frontal cortex of rats fed with açaí-en-riched diets[J]. Nutr Neurosci, 2017, 20(5): 305-315. DOI: 10.1080/1028415X.2015.1125654.
[12]Hanalioglu D, Hanalioglu S, Arango JI, et al. Didymin suppresses microglia pyroptosis and neuroinflammation through the Asc/Caspase-1/GSDMD pathway following experimenta-l intracerebral hemorrhage[J]. Childs Nerv Syst, 2023, 39(7): 1831-1849. DOI: 10.1007/s00381-023-05960-x. 
[13]Unlu MD, Asci H, Yusuf Tepebasi M, et al. The ameliorative effects of cannabidiol on methotrexate-induced neuroinflammation and neuronal apoptosis via inhibiting endoplasmic reticulum and mitochondrial stress[J]. J Biochem Mol Toxicol, 2024, 38(1): e23571. DOI: 10.1002/jbt.23571.
[14]Dogan Unlu M, Uysal D, Karakuyu NF, et al. Investigation of neuroprotective and therapeutic effects of cannabidiol in an acute coronary syndrome model[J]. Neurosci Lett, 2024, 825: 137689. DOI: 10.1016/j.neulet.2024.137689.
[15]Patel V, Abu-Hijleh F, Rigg N, et al. Cannabidiol protects striatal neurons by attenuating endoplasmic reticulum stress[J]. Cannabis Cannabinoid Res, 2023, 8(2): 299-308. DOI: 10.1089/can.2022.0090.
[16]Wang X, Lin C, Jin S, et al. Cannabidiol alleviates neuroinflammation and attenuates neuropathic pain via targeting FKBP5[J]. Brain Behav Immun, 2023, 111: 365-375. DOI: 10.1016/j.bbi.2023.05.008.
[17]Aychman MM, Goldman DL, Kaplan JS. Cannabidiol's neuroprotective properties and potential treatment of traumatic brain injuries[J]. Front Neurol, 2023, 14: 1087011. DOI: 10.3389/fneur.2023.1087011.

基金

云南省创新团队项目(202005AE160004);国家自然科学基金(81960223);云南省昆明医科大学联合专项(202301AY070001-163)

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