依达拉奉右莰醇对缺血性脑卒中大鼠神经功能及BDNF-AKT-CREB信号通路的影响

doi:10.3969/j.issn.1006-6233.2024.09.010

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摘要 目的: 探讨依达拉奉右莰醇(EDDE)对缺血性脑卒中(CIS)大鼠神经功能的影响,并基于脑源性神经营养因子(BDNF)-蛋白激酶B(AKT)-cAMP反应元素结合蛋白(CREB)信号通路初步探讨可能的作用机制。方法: 将大鼠随机分为5组:假手术组(Sham组)、CIS模型组(CIS组)、EDDE低剂量组(EDDE-L)、EDDE高剂量组(EDDE-H组)、尼莫地平组;采用mNSS评分法进行神经功能评估,2,3,5-三苯基氯化四氮唑(TTC)染色检测大鼠脑梗死面积,尼式染色观察大鼠脑组织病理损伤情况,同时检测脑组织白细胞介素-1β(IL-1β)、白介素-6(IL-6)、超氧化物歧化酶(SOD)、丙二醛(MDA)含量、BDNF mRNA、AKT mRNA、CREB mRNA以及BDNF、AKT、CREB蛋白表达情况。结果: 与Sham组相比,CIS组大鼠神经功能评分、脑梗死面积、细胞凋亡率以及IL-1β、IL-6、MDA含量显著增加,而SOD含量、BDNF mRNA、AKT mRNA、CREB mRNA、BDNF蛋白、AKT蛋白、CREB蛋白表达均显著减少(P<0.05),与此同时大脑皮层细胞数量减少、空泡较多,细胞核出现固缩现象;与CIS组相比,EDDE-L组、EDDE-H组和尼莫地平组神经功能评分、脑梗死面积、细胞凋亡率以及IL-1β、IL-6、MDA含量显著减少,而SOD含量、BDNF mRNA、AKT mRNA、CREB mRNA、BDNF蛋白、AKT蛋白、CREB蛋白表达均显著增加(P<0.05),大脑皮层细胞结构也相对完整;其中EDDE-H组和尼莫地平组效果更明显(P<0.05)。结论: EDDE可能通过激活BDNF-AKT-CREB通路,抑制炎症因子表达,降低氧化应激水平,减少CIS大鼠脑梗死面积,改善其神经功能损伤。

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	赵学栋
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关键词 ：依达拉奉右莰醇, BDNF-AKT-CREB信号通路, 缺血性脑卒中, 神经功能

Abstract：Objective: To investigate the effect of edaravone dexborneol (EDDE) on neurological function in rats with cerebral ischemic stroke (CIS), and to preliminarily explore the possible mechanism of BDNF (brain-derived neurotrophic factor) -AKT-CREB (cAMP response element binding protein) signaling pathway.Methods: Rats were randomly divided into five groups:sham operation group (sham group), CIS model group (CIS group), EDDE low dose group (EDDE-L group), EDDE high dose group (EDDE-H group), and nimodipine group; neural function was assessed by mNSS scoring method, and the area of cerebral infarction was detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining in the rat, and the area of ni The pathological damage of rat brain tissue was observed, and the interleukin-1β (IL-1β), interleukin-6 (IL-6), superoxide dismutase (SOD), malondialdehyde (MDA) content, BDNF mRNA, AKT mRNA, CREB mRNA, and BDNF, AKT, CREB protein expression of brain tissue were also detected.Results: Compared with the sham group, the neurological function score, cerebral infarction area, apoptosis rate and the contents of IL-1β, IL-6, and MDA in the CIS group were significantly increased, while the expressions of SOD, BDNF mRNA, AKT mRNACREB mRNA, BDNF protein, AKT protein, CREB protein were significantly decreased (P<0.05). At the same time the number of cells in the cerebral cortex decreases, vacuoles are more numerous and nuclei appear to be consolidated. Compared with the CIS group, the neurological function scores, cerebral infarct area, apoptosis rate, and the contents of IL-1β, IL-6, and MDA were significantly reduced in the EDDE-L, EDDE-H, and nimodipine groups, whereas the contents of SOD, the BDNF mRNA, AKT mRNA, CREB mRNA, and the expression of BDNF protein, AKT protein, and CREB protein were all significantly increased ( P<0.05), and the cellular structure of the cerebral cortex was also relatively intact; among them, the effect was more obvious in the EDDE-H and nimodipine groups (P<0.05).Conclusion: EDDE may reduce the area of cerebral infarction and improve the neurological impairment in CIS rats by activating the BDNF-AKT-CREB pathway, inhibiting the expression of inflammatory factors, and reducing the level of oxidative stress.

Key words： Edaravone dexborneol BDNF-AKT-CREB signaling pathway Ischemic stroke Neurological function

基金资助:河北省中医药管理局2021年度中医药类科研计划课题,(编号:2021314)

通讯作者: 李宝栋

引用本文:

赵学栋, 刘景峰, 金美美, 李宝栋. 依达拉奉右莰醇对缺血性脑卒中大鼠神经功能及BDNF-AKT-CREB信号通路的影响[J]. 河北医学, 2024, 30(9): 1467-1472.
ZHAO Xuedong, LIU Jingfeng, JIN Meimei, et al. Effects of Edaravone Dexborneol on Neural Function and BDNF-AKT-CREB Signaling Pathway in Ischemic Stroke Rats. HeBei Med, 2024, 30(9): 1467-1472.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2024.09.010 或 http://www.hbyxzzs.cn/CN/Y2024/V30/I9/1467

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