中国临床神经外科杂志2024,Vol.29Issue(8) :473-477.DOI:10.13798/j.issn.1009-153X.2024.08.007

吡咯喹啉醌对颅脑损伤小鼠的神经保护作用

Protective effect of pyrroloquinoline quinone on mice after traumatic brain injury

王凯 王利 伊西才 王彦刚
中国临床神经外科杂志2024,Vol.29Issue(8) :473-477.DOI:10.13798/j.issn.1009-153X.2024.08.007

吡咯喹啉醌对颅脑损伤小鼠的神经保护作用

Protective effect of pyrroloquinoline quinone on mice after traumatic brain injury

王凯 1王利 1伊西才 1王彦刚1
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作者信息

  • 1. 710032西安,空军军医大学第一附属医院神经外科
  • 折叠

摘要

目的 探讨吡咯喹啉醌(PQQ)对颅脑损伤(TBI)小鼠的保护作用及潜在机制.方法 将60只C57BL/6小鼠随机分为假手术组、TBI组和PQQ组,每组20只.使用可控皮层冲击方法建立TBI模型.PQQ组伤前30 min腹腔注射溶PQQ(10 mg/kg),假手术组和TBI组腹腔注射等量生理盐水.伤后24 h,采用神经功能评分法评估小鼠神经功能,使用干湿重法检测脑含水量,采用TUNEL染色检测神经元凋亡,采用ELISA法检测脑组织白介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)水平,采用免疫印迹法检测脑组织caspase3、Notch受体胞内段(NICD)、发状分裂相关增强子1(HES-1)、小胶质细胞离子钙结合衔接分子1(IBA1)的蛋白表达水平.结果 与假手术组比较,TBI组小鼠脑含水量及神经功能学评分均明显升高(P<0.05),脑组织IL-1β及TNF-α含量均明显升高(P<0.05),脑组织TUNEL阳性细胞率明显升高(P<0.05),脑组织NICD、HES-1、IBA-1和活化caspase3达量水平明显增加(P<0.05).与TBI组比较,PQQ组小鼠脑含水量及神经功能学评分均明显减少(P<0.05),脑组织IL-1β水平及TNF-α水平均明显降低(P<0.05),脑组织TUNEL阳性细胞率明显降低(P<0.05),脑组织NICD、HES-1达量水平明显增加,但脑组织IBA-1和活化caspase3表达水平明显降低(P<0.05).结论 PQQ可减轻TBI小鼠脑水肿、炎症反应和神经元凋亡,改善神经功能,从而发挥脑保护作用,其机制可能与激活Notch信号通路有关.

Abstract

Objective To explore the protective effect and potential mechanism of pyrroloquinoline quinone (PQQ) on mice with traumatic brain injury (TBI).Methods Sixty C57BL/6 mice were randomly divided into sham operation group,TBI group and PQQ group,with 20 mice in each group.The TBI model was established by controlled cortical impact.The mice in the PQQ group were intraperitoneally injected with PQQ (10 mg/kg) 30 minutes before injury,while the mice in the sham operation and the TBI groups were intraperitoneally injected with the same amount of normal saline.At 24 hours after injury,the neurological function of mice was evaluated by neurological function score,the brain water content was detected by the dry-wet weight method,neuronal apoptosis was detected by TUNEL staining,the levels of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in brain tissue were detected by ELISA,and the protein expression levels of caspase 3,Notch receptor intracellular domain (NICD),hairy and enhancer of split 1 (HES-1),and ionized calcium-binding adapter molecule 1 (IBA1) of microglia in brain tissue were detected by Western blotting.Results Compared with the sham operation group,the brain water content and neurological function score of the TBI group were significantly increased (P<0.05),the contents of IL-1βand TNF-αin brain tissue were significantly increased (P<0.05),the rate of TUNEL positive cells in brain tissue was significantly increased (P<0.05),and the expression levels of NICD,HES-1,IBA-1 and activated caspase3 in brain tissue were significantly increased (P<0.05).Compared with the TBI group,the brain water content and neurological function score of the PQQ group were significantly decreased (P<0.05),the levels of IL-1βand TNF-αin brain tissue were significantly decreased (P<0.05),the rate of TUNEL positive cells in brain tissue was significantly decreased (P<0.05),the expression levels of NICD and HES-1 in brain tissue were significantly increased,but the expression levels of IBA-1 and activated caspase3 in brain tissue were significantly decreased (P<0.05).Conclusion PQQ can alleviate brain edema,inflammatory response and neuronal apoptosis in TBI mice,improve neurological function,and thus exert a neuroprotective effect.Its mechanism may be related to the activation of the Notch signaling pathway.

关键词

颅脑损伤/吡咯喹啉醌/炎症反应/脑水肿/神经元凋亡/小鼠

Key words

Traumatic brain injury/Pyrroloquinoline quinone/Inflammation/Brain edema/Neuronal apoptosis/Mice

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出版年

2024
中国临床神经外科杂志
广州军区武汉总医院

中国临床神经外科杂志

CSTPCD
影响因子:0.781
ISSN:1009-153X
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