摘要
目的探讨血红蛋白氧载体(HBOC)与依达拉奉(EDA)联合应用对急性脑梗死(ACI)模型大鼠神经元的保护作用及机制。方法通过在线数据库、网络构建和富集分析,获取HBOC与依达拉奉联合治疗ACI的关键靶点和潜在的作用机制;将120只SD雄性大鼠均分为假手术组、模型组、HBOC治疗组、EDA治疗组、HBOC联合EDA治疗组(联合治疗组),后4组大鼠建立大脑中动脉梗死(MCAO)模型,建模3 h后,各组大鼠分别注射生理盐水(6 mL/kg)、HBOC(6 mL/kg)、EDA(1.5 mL/kg)、HBOC(6 mL/kg)联合EDA(1.5 mL/kg);于造模24 h时,记录各组大鼠的神经功能评分、观察脑缺血梗死灶与脑水肿体积、神经元形态,采用流式细胞术及Western blot检测生物信息学分析出的关键靶点,探讨HBOC联合EDA对ACI模型大鼠的神经保护作用及可能机制。结果网络药理学分析显示HBOC联合EDA治疗ACI有106个共同靶点,生物信息学显示其神经保护作用可能主要是由白细胞介素-17(IL-17)信号通路、缺氧诱导因子-1(HIF-1)信号通路、肿瘤坏死因子(TNF)信号通路等途径介导,并获得关键通路上存在半胱氨酸天冬氨酸蛋白酶3(Caspase-3)、缺氧诱导因子-1α(HIF-1α)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)等核心靶点;生物学实验结果显示,与模型组、HBOC治疗组及EDA治疗组相比,联合治疗组的神经功能评分降低、梗死灶体积百分比与脑水肿体积百分比减少、细胞出现碎片化核仁和凋亡小体较少、细胞排列较规则、具有更少的细胞坏死和细胞凋亡比例,药物联合治疗核心靶点Caspase-3、HIF-1α,IL-6、TNF-α的表达也降低,差异有统计学意义(P<0.05)。结论HBOC联合EDA能改善ACI模型大鼠的神经功能缺损症状,显著减少梗死灶体积及脑水肿体积,其机制可能与联合用药减轻ACI时大鼠脑组织的炎症反应与细胞凋亡有关。
Objective To investigate the neuroprotective effect and possible mechanism of hemoglobin oxygen carrier(HBOC)combined with edaravone(EDA)on acute cerebral infarction(ACI)in rats.Methods The key targets and potential mechanisms of HBOC combined with EDA in the treatment of ACI were analyzed by online database,network construction and enrichment analysis.A total of 120 SD male rats were divided into sham operation group,model group,HBOC treatment group,EDA treatment group,HBOC combined with EDA treatment group(combined treatment group).Except for the sham operation group,the middle cerebral artery infarction(MCAO)model of rats was established in the other groups.After 3 hours of model establishment,rats in each group were injected with normal saline(6 mL/kg),HBOC(6 mL/kg),edaravone injection(1.5 mL/kg)and HBOC(6 mL/kg)combined with EDA.The neurological function scores of rats in each group were recorded,the volume of cerebral infarction and cerebral edema,and the morphology of neuronal cells were observed.The key targets analyzed by bioinformatics were detected by flow cytometry and Western blot,and the neuroprotective effect and possible mechanism of HBOC combined with edaravone on ACI in rats were discussed.Results Network pharmacology analysis showed that there were 106 common targets for HBOC combined with EDA in the treatment of ACI,and the bioinformatics showed that its neuroprotective effect may be mainly mediated by interleukin-17(IL-17)signaling pathway,hypoxia-inducible factor-1(HIF-1)signaling pathway,tumor necrosis factor(TNF)signaling pathway and other pathways.The core targets of Caspase-3,HIF-1α,IL-6,TNF-α,and other key pathways were obtained.The results showed that there were core targets such as Caspase-3,HIF-1α,IL-6,and TNF-αin the key pathways.The results of biological experiments showed that compared with the model group,HBOC treatment group and EDA treatment group,the neurological function score of the combined treatment group decreased,the percentage of infarct volume and the percentage of
作者
周正龙
胡俞成
韩润敏
彭瀚
杨华
向欣
ZHOU Zhenglong;HU Yucheng;HAN Runmin;PENG Han;YANG Hua;XIANG Xin(Department of Neurosurgery,the Affiliated Hospital of Guizhou Medical University,Guiyang 550004,Guizhou,China;Department of Neurosurgery,Jiyuan Hospital of Traditional Chinese Medicine,Jiyuan 459000,Henan,China)
出处
《贵州医科大学学报》
CAS
2023年第5期497-507,共11页
Journal of Guizhou Medical University
基金
国家自然科学基金(81660239)。
关键词
急性脑梗死
血红蛋白氧载体
依达拉奉
联合治疗
acute cerebral infarction(ACI)
hemoglobin oxygen carrier(HBOC)
edaravon(EDA)
combination therapy
