首页|基于NF-κB/ICAM-1通路探讨大黄酚对重型颅脑损伤大鼠神经功能的作用

基于NF-κB/ICAM-1通路探讨大黄酚对重型颅脑损伤大鼠神经功能的作用

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目的 基于核因子κB(NF-κB)/细胞间粘附分子-1(ICAM-1)通路探讨大黄酚(Chr)对重型颅脑损伤(sTBI)大鼠神经功能的作用。方法 大鼠分为sTBI组、对照组、Chr低剂量组、Chr高剂量组、依达拉奉组、Chr高剂量+NF-κB激动剂脂多糖(LPS)组,每组18只。除对照组外,其它组大鼠均通过改良Freeney's自由落体法构建sTBI模型,建模6 h后开始处理,给药1次/d,持续7 d。检测大鼠改良神经功能缺损评分(mNSS)、逃避潜伏期、穿越平台次数、脑含水量变化;HE染色检测脑组织的病理学变化;ELISA检测脑组织中白细胞介素(IL)-6、IL-12、肿瘤坏死因子-α(TNF-α)水平;TUNEL染色检测脑组织细胞凋亡;Western blot检测脑组织中Bcl-2相关X蛋白(Bax)、含半胱氨酸的天冬氨酸蛋白水解酶-9(Caspase-9)、p-NF-κB p65、ICAM-1蛋白水平。结果 与对照组比较,sTBI组大鼠脑组织损伤严重,mNSS评分、脑含水量、脑组织中IL-6、IL-12、TNF-α水平、细胞凋亡率及Bax、Caspase-9、p-NF-κB p65、ICAM-1蛋白水平升高,逃避潜伏期延长,穿越平台次数减少(均P<0。05)。与sTBI组比较,Chr低、高剂量组、依达拉奉组脑组织细胞形态改善,mNSS评分、脑含水量、脑组织中IL-6、IL-12、TNF-α水平、细胞凋亡率及Bax、Caspase-9、p-NF-κB p65、ICAM-1蛋白水平降低,逃避潜伏期缩短,穿越平台次数增加(均P<0。05)。LPS可逆转高剂量Chr对sTBI大鼠的影响。结论 Chr改善sTBI大鼠神经功能,抑制神经炎症及细胞凋亡的机制可能与下调NF-κB/ICAM-1通路有关。
Effect of Chrysophanol on Neurological Function in Severe Traumatic Brain Injury Rats Based on the NF-κB/ICAM-1 Pathway
Objective To investigate the improvement effect of chrysophanol(Chr)on neurological function in rats with se-vere traumatic brain injury(sTBI)based on the nuclear factor-κB(NF-κB)/intercellular adhesion molecule-1(ICAM-1)path-way.Methods Rats were separated into sTBI group,control group,Chr low-dose group,Chr high-dose group,edaravone group,Chr high-dose+NF-κB agonist lipopolysaccharide(LPS)group,with 18 rats in each group.Except for the control group,rats in all other groups were used to construct sTBI models using the improved Freeney's free fall method.Drugs were given once a day for 7 days after modeling for 6 hours.The modified neurological deficit score(mNSS),escape latency,number of platform crossing,and changes in brain water content were detected in rats.HE staining was applied to detect pathological changes in brain tissue.ELISA was applied to detect levels of interleukin(IL)-6,IL-12,and tumor necrosis factor-α(TNF-α)in brain tis-sue.TUNEL staining was applied to detect apoptosis in brain tissue cells.Western blot was applied to detect Bcl-2-associated X protein(Bax),Caspase-9,p-NF-κB p65,and ICAM-1 protein in brain tissue.Results Compared with the control group,severe brain tissue damage of the sTBI group rats,the mNSS score,brain water content,levels of IL-6,IL-12,TNF-α in brain tissue,cell apoptosis rate,and Bax,Caspase-9,p-NF-κB p65,ICAM-1 proteins increased,the escape latency extended,the number of platform crossing decreased(all P<0.05).Compared with the sTBI group,the brain tissue cell morphology in the Chr low-dose,Chr high-dose group,and edaravone group improved.The mNSS score,brain water content,levels of IL-6,IL-12,TNF-α in brain tissue,cell apoptosis rate,and Bax,Caspase-9,p-NF-κB p65,ICAM-1 proteins decreased,the escape latency shortened,the number of platform crossing increased(all P<0.05).LPS could reverse the effect of high-dose Chr on sTBI rats.Conclusion The mechanism by which chrysophanol improves neurological function,inhibits neuroinflammation and cell apoptosis in sTBI rats may be related to the downregulation of the NF-κB/ICAM-1 pathway.

chrysophanolnuclear factor-KB/intercellular adhesion molecule-1 pathwaysevere traumatic brain injuryneuroinflammationneurological functionapoptosis

刘彪、郑慧军、杜康、徐澳磊

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河南省中医院(河南中医药大学第二附属医院)神经外科,郑州 450002

河南中医药大学骨伤学院,郑州 450002

大黄酚 核因子κB/细胞间粘附分子-1通路 重型颅脑损伤 神经炎症 神经功能 凋亡

2024

华中科技大学学报(医学版)
华中科技大学

华中科技大学学报(医学版)

CSTPCD北大核心
影响因子:1.443
ISSN:1672-0741
年,卷(期):2024.53(6)