摘要
目的 探讨布洛芬调节核因子E2相关因子2(Nrf2)/非糖基化的x CT(SLC7A11)/谷胱甘肽过氧化物酶4(GPX4)信号通路对缺血性脑中风(IS)大鼠神经保护的作用。方法 48只以大脑中动脉梗死模型复制IS大鼠,将IS大鼠随机分为IS组、治疗组(30 mg/kg布洛芬)、抑制剂组(30 mg/kg ML385)、治疗+抑制剂组(30 mg/kg布洛芬+30 mg/kg ML385),其中以仅分离血管但不结扎的12只大鼠作为假手术组。干预结束后,对大鼠进行神经功能评分,检测大鼠脑梗死率以及脑水肿含量;取出大鼠脑组织,观察神经元形态学变化、检测铁离子含量变化以及Nrf2/SLC7A11/GPX4信号通路相关因子表达。结果 与假手术组相比,IS组神经功能评分、脑梗死率、脑水肿含量、铁离子含量显著增加,Nrf2、SLC7A11、GPX4表达显著降低(P <0.05);与IS组相比,治疗组神经功能评分、脑梗死率、脑水肿含量、铁离子含量显著下降,Nrf2、SLC7A11、GPX4表达显著增加(P <0.05);抑制剂组逆转了治疗组对IS大鼠神经保护。结论 布洛芬可以保护IS大鼠神经受损,可能与激活Nrf2/SLC7A11/GPX4信号通路有关。
Objective To investigate the neuroprotective effect of ibuprofen on ischemic stroke(IS) rats by regulating nuclear factor E2-related factor 2(Nrf2)/non-glycosylated xCT(SLC7A11)/glutathione peroxidase 4(GPX4) signaling pathway.Methods Forty eight IS rats prepared under the middle cerebral artery infarction model were randomly divided into IS group,treatment group(30 mg/kg ibuprofen),inhibitor group(30 mg/kg ML385),and treatment + inhibitor group(30 mg/kg ibuprofen + 30 mg/kg ML385).Another 12 rats were set as a sham-operated group,where the rats were prepared only by separating the blood vessels instead of ligating them.After intervention,the neurological function of the rats was scored,and the rate of cerebral infarction and the content of cerebral edema were detected.After that,the rat brain tissue was removed to observe the morphological changes of neurons,measure the contents of iron ion and detect the expression of proteins related to the Nrf2/SLC7A11/GPX4 signaling pathway.Results Compared with the sham operation group,the neurological function score,cerebral infarction rate,cerebral edema content and iron ion content in IS group were significantly increased,and the expressions of Nrf2,SLC7A11 and GPX4 were obviously decreased(P<0.05);compared with the IS group,the neurological function score,cerebral infarction rate,cerebral edema content and iron ion content in the treatment group were obviously decreased,and the expressions of Nrf2,SLC7A11,and GPX4 were significantly increased as well.The neuroprotection of the treatment group on IS rats was reversed in the inhibitor group.Conclusion Ibuprofen can protect nerve damage in IS rats,which may be related to the activation of Nrf2/SLC7A11/GPX4 signaling pathway.
作者
何俊荣
刘仔
陈锡培
HE Junrong;LIU Zai;CHEN Xipei(Dongguan Hospital of Guangzhou University of Traditional Chinese Medicine,Dongguan 523000,China)
出处
《实用医学杂志》
CAS
北大核心
2023年第15期1888-1892,共5页
The Journal of Practical Medicine
基金
广东省基础与应用基础研究基金地域联合基金项目(地区培育项目)(编号:21202107190000227)。
