抑制AQP4对脑缺血再灌注损伤模型小鼠Bax、Bcl-2、Caspase-3表达的影响  

Effect of AQP4 inhibition on the expression of Bax,Bcl-2,and Caspase-3 in mice modeled with cerebral ischemia-reperfusion injury

作　　者：黄玲晓 莫圣龙 简崇东[1] 商敬伟 HUANG Ling-Xiao;MO Sheng-Long;JIAN Chong-Dong(Department of Neurology,Afiliated Hospital of Youjiang Medical University for Nationalities,Baise 533000,Guangxi,China)

机构地区：[1]右江民族医学院附属医院神经内科,广西百色533000 [2]右江民族医学院研究生学院 [3]河池市人民医院神经内科

出　　处：《吉林医学》2025年第4期763-768,共6页Jilin Medical Journal

基　　金：国家自然科学基金[项目编号:81860244,82160254];广西研究生教育创新计划项目[项目编号:YCSW2023494];右江民族医学院附属医院高层次人才科研项目[项目编号:R20213001,R20196308];广西高校中青年教师科研基础能力提升项目[项目编号:2025KY0547];百色市科学研究与技术开发计划课题[项目编号:百科20250342]。

摘　　要：目的:探讨抑制AQP4对脑缺血再灌注损伤(I/R)模型小鼠因子Bcl-2相关x蛋白(Bax)、因子B淋巴细胞瘤-2(Bcl-2)、天冬氨酸蛋白水解酶-3(Caspase-3)表达的影响。方法:45只C57BL/6J小鼠随机分为假手术组(Sham组)、模型组(I/R组)、给药组(AQP4抑制组),每组15只。建立小鼠脑缺血再灌注损伤模型,缺血1 h后再灌注,给药组立即给予AQP4抑制剂AER-2712 mg/kg腹腔注射,Sham组与I/R组给予等体积生理盐水腹腔注射,给药后24 h取材。采用Longa评分评估小鼠神经功能损伤情况;TTC染色观察小鼠脑梗死面积;Western印迹法及免疫荧光染色检测Bax、Bcl-2、Caspase-3蛋白表达的情况。结果:①与Sham组比较,I/R组小鼠神经功能损伤症状显著加重,差异有统计学意义(P<0.05);TTC染色可见大面积脑梗死;Western印迹检测显示小鼠脑组织Bax、Caspase-3蛋白表达水平显著升高,Bcl-2蛋白表达水平显著下降,差异有统计学意义(P<0.05);免疫荧光染色显示Bcl-2表达降低,Bax、Caspase-3表达升高。②与I/R组比较,AQP4抑制组小鼠神经功能缺损症状显著减轻,差异有统计学意义(P<0.05);脑梗死面积减小;Western印迹检测显示小鼠脑组织Bax、Caspase-3蛋白表达水平显著降低,Bcl-2蛋白表达水平显著升高,差异有统计学意义(P<0.05);免疫荧光染色显示Bcl-2表达升高,Bax、Caspase-3表达降低。结论:抑制AQP4可抑制I/R小鼠神经细胞凋亡,减少脑细胞组织梗死面,修复神经细胞,改善神经功能缺损。Objective To explore the impact of AQP4 inhibition on the expression of Bax,Bcl-2,and Caspase-3 in mice with cerebral ischemia-reperfusion injury(I/R).Methods Forty-five C57BL/6J mice were randomly divided into three groups:the Sham operation group(Sham group),the model group(I/R group),and the drug administration group(AQP4 inhibitors group),with Fifteen mice in each group.A model of middle cerebral artery occlusion was established,followed by one hour of ischemia and subsequent reperfusion.Immediately,the control group received an intraperitoneal injection of the AQP4 inhibitor AER-271 at 2 mg/kg,while the Sham and model groups received an equivalent volume of saline.Tissue samples were collected 24 hours post-treatment.The neurological function was assessed using the Longa score,the area of cerebral infarction was observed by TTC staining,and the expression levels of Bax,Bcl-2,and Caspase-3 proteins were measured by Western blot and immunofluorescence staining.Results①Compared with the Sham group,the model group exhibited significantly worsened neurological function(P<0.05),extensive cerebral infarction as shown by TTC staining,significantly increased expression levels of Bax and Caspase-3 proteins,and a notable decrease in Bcl-2 protein expression(P<0.05)as determined by Western blot.Immunofluorescence staining showed lower expression of Bcl-2 and higher expression of BAX and Caspase-3.②Relative to the model group,the control group showed improved neurological function(P<0.05),reduced cerebral infarction area,decreased expression levels of Bax and Caspase-3 proteins,and in-increased Bcl-2 protein expression(P<0.05)as assessed by Western blot.Immunofluorescence staining indicated higher expression of Bcl-2 and lower expression of Bax and Caspase-3.Conclusions Inhibition of AQP4 can suppress neuronal apoptosis and mitigate cerebral ischemia-reperfusion injury,offering neuroprotective effects.

关 键 词：缺血/再灌注 细胞凋亡 BCL-2 BAX CASPASE-3 

分 类 号：R743.3[医药卫生—神经病学与精神病学]