内蒙古医学杂志2024,Vol.56Issue(3) :264-268,275,封2.DOI:10.16096/J.cnki.nmgyxzz.2024.56.03.002

丙泊酚通过Nrf2通路对缺血性脑卒中小鼠发挥脑保护作用的机制研究

The Research of the Protective Effect of Propofol on the Brain of Ischemic Stroke Mice Through Nrf2 Pathway

李淑凡 刘志慧 王燕燕 温家康
内蒙古医学杂志2024,Vol.56Issue(3) :264-268,275,封2.DOI:10.16096/J.cnki.nmgyxzz.2024.56.03.002

丙泊酚通过Nrf2通路对缺血性脑卒中小鼠发挥脑保护作用的机制研究

The Research of the Protective Effect of Propofol on the Brain of Ischemic Stroke Mice Through Nrf2 Pathway

李淑凡 1刘志慧 1王燕燕 2温家康3
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作者信息

  • 1. 内蒙古医科大学包头临床医学院,内蒙古包头 014040
  • 2. 包头医学院中心临床医学院,内蒙古包头 014040
  • 3. 内蒙古医科大学内蒙古临床医学院,呼和浩特 010017
  • 折叠

摘要

目的 探讨丙泊酚处理对缺血性脑卒中小鼠脑组织炎症及氧化应激的保护作用和神经功能的改善作用,并阐明其作用机制.方法 选取48只C57小鼠,随机分为假手术组(Sham组)、假手术+丙泊酚组(Sham+P组)、缺血性脑卒中组(IS组)和缺血性脑卒中+丙泊酚组(IS+P组),每组12只.IS组和IS+P组小鼠采用MCAO模型线栓法建立缺血性脑卒中模型;Sham+P组和IS+P组于造模后即刻腹腔注射30 mg/kg丙泊酚,12 h后重复给药一次;Sham组和IS组于腹腔注射等量生理盐水.各组小鼠于造模成功的24 h后进行评分,采用HE图像观察小鼠脑形态表现,采用相关试剂盒检测各组小鼠脑组织中炎症因子、氧化应激因子以及神经损伤相关因子的水平,采用Western Blot法检测小鼠脑组织中Nrf2蛋白表达水平.结果 与Sham组相比较,Sham+P组小鼠各相关指标均未见明显差异(P>0.05),IS组小鼠神经功能缺损评分明显升高(P<0.05),脑组织病理损伤较之明显改善(P<0.05),血清中的TNF-a、IL-6显著增加(P<0.05),脑组织SOD水平显著降低,MDA水平、NSE及GFAP水平均显著升高(P<0.05),Nrf2蛋白表达显著升高(P<0.05);与IS组比较,IS+P组小鼠神经功能评分降低(P<0.05),脑组织病理损伤改善明显,炎症细胞浸润减少(P<0.05),血清中TNF-a及IL-6的含量显著降低(P<0.05),脑组织SOD水平升高,MDA、NSE及GFAP水平下降(P<0.05),Nrf2蛋白表达水平降低显著(P<0.05).结论 丙泊酚处理可抑制缺血性脑卒中小鼠脑组织炎症免疫反应和氧化应激,改善小鼠神经功能损伤,其机制可能与调控Nrf2通路有关.

Abstract

Objective To explore the protective effect of propofol on inflammation and oxidative stress in brain tissue of ischemic stroke mice and to improve nerve function,and to clarify its mechanism.Methods Forty-eight C57 mices were divided into Sham group,Sham+P(propofol)group,IS(Ischemic stroke)group and IS+P group randomly,with 12 mices in each group.Mice in the IS group and the IS+P group were treat-ed with MCAO model to establish ischemic stroke model.The Sham+P group and the IS+P group were in-traperitoneally injected with 30 mg/kg propofol immediately after modeling,and the administration was repeated 12h later.The Sham group and the IS group were intraperitoneally injected with equal volume of normal saline.After 24 hours,mice in each group were scored with neurological deficit.HE staining method was used to ob-serve the pathological morphology of brain tissue of mice in each group,and the levels of inflammatory factors,oxidative stress factors and nerve injury related factors in brain tissue of mice in each group were detected with relevant kits.The expression of nuclear factor E2-related factor 2(Nrf2)protein in the brain of mice in each group was detected by Western Blotting.Results Compared with the Sham+P group,there were no differ-ences in all indexes of mice in the Sham group(P>0.05),the neurological function deficit score of mice in IS group was significantly increased(P<0.05),the pathological injury and inflammatory infiltration of brain were significant(P<0.05),and the TNF-a and IL-6 were increased significantly(P<0.05).The level of SOD in brain was significantly decreased,the levels of MDA,NSE and GFAP were significantly increased(P<0.05),and the expression of Nrf2 was significantly increased(P<0.05).Compared with the IS group,the neurological function deficit score of mice in the IS+P group was significantly decreased(P<0.05),the histopathological injury was significantly improved,the inflammatory cell infiltration was decreased(P<0.05),the serum TNF-α and IL-6 contents were significantly decreased(P<0.05),and the level of SOD in brain was increased.The levels of MDA,NSE and GFAP were decreased(P<0.05),and the expression of Nrf2 protein was de-creased(P<0.05).Conclusion The treatment of propofol can inhibit the inflammatory immune response and oxidative stress in the brain of mice with ischemic stroke,and improve the neurological damage of mice,the mechanism of which may be related to the regulation of Nrf2 pathway.

关键词

丙泊酚/缺血性脑卒中/氧化应激/抗炎/抗氧化/Nrf2

Key words

propofol/ischemic stroke/oxidative stress/anti-inflammatory/anti-oxidant/Nrf2

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基金项目

内蒙古医科大学联合项目(YKD2021LH063)

内蒙古医科大学研究生卓越人才计划项目(YKD2023ZY001)

出版年

2024
内蒙古医学杂志
内蒙古自治区医学会

内蒙古医学杂志

影响因子:0.537
ISSN:1004-0951
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