腺苷预处理对脑缺血再灌注损伤大鼠脑保护作用及机制  

Protective effect of adenosine pretreatment on the brain of rats with cerebral ischemia-reperfusion injury and related mechanisms

作　　者：李国栋 谭军[2] 薛倩倩 栗延伟[2] 裴科阳 LI Guodong;TAN Jun;XUE Qianqian;LI Yanwei;PEI Keyang(Xinxiang Medical University,Xinxiang 453003,Henan Province,China;The Third Affiliated Hospital of Xinxiang Medical University,Xinxiang 453000,Henan Province,China;The Second Affiliated Hospital of Xinxiang Medical University,Xinxiang 453000,Henan Province,China)

机构地区：[1]新乡医学院,河南新乡453003 [2]新乡医学院第三附属医院神经内二科,河南新乡453000 [3]新乡医学院第二附属医院神经内科二病区,河南新乡453000

出　　处：《新乡医学院学报》2025年第1期9-14,共6页Journal of Xinxiang Medical University

基　　金：河南省医学科技攻关计划项目联合共建项目(编号:LHGJ20230546)。

摘　　要：目的探讨腺苷预处理(AP)对脑缺血再灌注(IR)损伤大鼠脑保护作用及机制。方法将36只健康雄性Sprague Dawley大鼠按随机数字表法分为假手术组、IR组、AP组,每组12只。IR组和AP组大鼠采用线栓法构建大脑IR损伤模型;假手术组大鼠仅分离颈动脉,不结扎血管。AP组大鼠造模前每天腹腔注射2 mL腺苷注射液,连续3 d;假手术组及IR组大鼠每天腹腔注射2 mL生理盐水,连续3 d。栓塞2 h后恢复脑血流灌注,24 h后采用神经行为学评分评估各组大鼠神经行为。完成神经行为学评估后处死各组大鼠,取出脑组织,采用氯化三苯四氮唑染色法检测脑组织梗死体积占比,二氢乙锭染色法检测大鼠脑组织中活性氧(ROS)水平,比色法检测大鼠脑组织中亚铁离子水平,实时荧光定量聚合酶链式反应法检测大鼠脑组织中谷胱甘肽过氧化物酶4(GPX4)、酰基辅酶A合成酶长链家族成员4(ACSL4)、烟酰胺腺嘌呤二核苷酸磷酸氧化酶1(NOX1)mRNA的相对表达量。结果假手术组、IR组、AP组大鼠神经行为学评分分别为0.000±0.000、2.333±0.876、1.416±0.669。3组大鼠神经行为学评分比较差异有统计学意义(F=40.288,P<0.05);IR组及AP组大鼠神经行为学评分显著高于假手术组,AP组大鼠神经行为学评分显著低于IR组(P<0.05)。假手术组、IR组、AP组大鼠脑梗死体积占比分别为(0.000±0.000)%、(38.531±3.483)%、(23.403±1.393)%。3组大鼠脑梗死体积占比比较差异有统计学意义(F=241.060,P<0.05);IR组及AP组大鼠脑梗死体积占比显著高于假手术组,AP组大鼠脑梗死体积占比显著低于IR组(P<0.05)。假手术组、IR组、AP组大鼠脑组织中ROS水平分别为13.582±0.067、30.083±0.969、26.502±0.569。3组大鼠脑组织中ROS水平比较差异有统计学意义(F=281.518,P<0.05);IR组及AP组大鼠脑组织中ROS水平显著高于假手术组,AP组大鼠脑组织中ROS水平显著低于IR组(P<0.01)。假手术组、IR组、AP组大鼠Objective To investigate the protective effects of adenosine pretreatment(AP)on the brain of rats with cerebral ischemia-reperfusion(IR)injury and related mechanisms.Methods Thirty-six healthy male Sprague Dawley rats were divided into sham operation group,IR group,and AP group by the random number table method,with 12 rats in each group.The cerebral IR injury model was constructed using the wire embolism method in IR and AP groups.For rats in the sham operation group,the carotid artery was isolated and vessels were not ligated.2 mL of adenosine injection and 2 mL of saline daily were intraperitoneally injected daily into rats in the AP group and those in the sham operation and IR groups for 3 consecutive days before modelling,respectively.Cerebral blood flow perfusion was restored 2 h after embolization,and 24 h later,the neurobehavioural assessment of rats in each group was made using a 5-point neurobehavioural score.After completing the neurobehavioral assessment,rats of all groups were executed,and the brain tissue was taken.The infarct volume ratio of brain tissue was calculated using 2,3,5-triphenyltetrazolium chloride(TTC)staining,the reactive oxygen species(ROS)level of brain tissue was detected by dihydroethylene staining,and the ferrous ion content in rat brain tissue was measured using the colorimetric method.Quantitative real-time polymerase chain reaction was used to detect the relative expression levels of mRNAs of glutathione peroxidase 4(GPX4),acyl-CoA synthetase long-chain family member 4(ACSL4),and nicotinamide adenine dinucleotide phosphate oxidase 1(NOX1)in rat brain tissue.Results The neurobehavioural scores of rats in sham operation,IR and AP groups were 0.000±0.000,2.333±0.876,and 1.416±0.669,respectively.Significant differences in the neurobehavioural score were observed among the three groups(F=40.288,P<0.05)The neurobehavioural scores of rats in IR and AP groups were significantly higher than those in the sham operation group,and the neurobehavioural scores of rats in the AP group wer

关 键 词：铁死亡 脑缺血再灌注损伤 谷胱甘肽过氧化物酶4 脂质过氧化 

分 类 号：R743.3[医药卫生—神经病学与精神病学]