中国病理生理杂志2024，Vol.40Issue(8)：1446-1454,9.DOI:10.3969/j.issn.1000-4718.2024.08.011
抑制水通道蛋白4表达对脑缺血再灌注模型小鼠自噬和凋亡的影响
Impact of inhibiting aquaporin 4 expression on autophagy and apoptosis in a mouse model of cerebral ischemia-reperfusion
摘要
Abstract
AIM:To investigate the impact of aquaporin 4(AQP4)expression inhibition on autophagy and apoptosis in a mouse model of cerebral ischemia-reperfusion(I/R)injury,and to elucidate its underlying mechanism.METHODS:Cerebral I/R injury was induced in mice via transient middle cerebral artery occlusion(tMCAO).Totally 60 mice were randomly divided into sham group,I/R group,AQP4 inhibition group,and 3-methyladenine(3-MA)group,with 15 mice in each group.Among them,the mice in sham and I/R groups received intraperitoneal injections of normal saline,while those in AQP4 inhibition group and 3-MA group received intraperitoneal injections of AER-271(2 mg·kg-1·d-1)and AER-271+3-MA(2 mg·kg-1·d-1)for 3 d,respectively,once per day.Longa score was adopted to assess the neu-rological function,and to record changes in body weight.Cerebral infarction volume and histopathological alterations were evaluated using hematoxylin-eosin staining.Western blot analysis was performed to determine the levels of AQP4,LC3-Ⅱ,P62 and cleaved caspase-3,while the LC3-Ⅱ,P62,cleaved caspase-3 and NeuN(neuronal marker)colocalization and expression assessment were conducted with immunofluorescence.RESULTS:The mice in I/R and AQP4 inhibition groups exhibited extensive cerebral infarction,cerebral edema,and elevated Longa scores.However,in comparision to I/R group,the mice in AQP4 inhibition group showed significantly reduced cerebral infarct volume,cerebral edema vol-ume,and Longa score(P<0.05).Additionally,in contrast to sham group,the mice in I/R group displayed increased ex-pression of AQP4,LC3-Ⅱ and cleaved caspase-3(P<0.01),accompanied by decreased body weight and P62 expression(P<0.05 or P<0.01).Furthermore,compared with I/R group,the mice in both AQP4 inhibition group and 3-MA group demonstrated a decrease in the expression levels of AQP4,LC3-Ⅱ and cleaved caspase-3(P<0.05 or P<0.01),along with increased body weight and P62 expression(P<0.05 or P<0.01).Nonetheless,no significant differences were ob-served between AQP4 inhibition group and 3-MA group regarding Longa score,cerebral infarct volume,body weight,and the expression of AQP4,LC3-Ⅱ,cleaved caspase-3 and P62.CONCLUSION:Inhibition of AQP4 expression signifi-cantly reduces cerebral infarction area and nerve injury severity in tMCAO mice.Moreover,AQP4 expression inhibition decelerates autophagy and apoptosis after cerebral infarction,with the additional autophagy inhibitor showing no notable impact on the protective effect of AQP4 inhibition.关键词
急性缺血性脑卒中/细胞凋亡/水通道蛋白4/细胞自噬/脑缺血再灌注损伤Key words
acute ischemic stroke/apoptosis/aquaporin 4/autophagy/cerebral ischemia-reperfusion injury分类
医药卫生引用本文复制引用
莫圣龙,朱海燕,陆志成,莫嘉祺,彭晓靖,唐丽娜,杨成敏,简崇东,商敬伟..抑制水通道蛋白4表达对脑缺血再灌注模型小鼠自噬和凋亡的影响[J].中国病理生理杂志,2024,40(8):1446-1454,9.基金项目
国家自然科学基金资助项目(No.81860244 （）
No.82160254) （）
右江民族医学院附属医院高层次人才科研项目(No.R20213001) （No.R20213001）
百色市科学研究与技术开发计划课题(百科20224117号) （百科20224117号）
广西研究生教育创新计划项目(No.YCSW2023494) （No.YCSW2023494）
