紫草酸甲酯抑制海马Nox4介导的铁死亡改善小鼠术后学习记忆障碍  

Paederosidic acid methyl ester inhibits hippocampal Nox4-mediated ferroptosis and improves postoperative learning and memory in mice

作　　者：刘铁龙 亓文强 江洪洋 王瑞雪 代志刚[1] 殷姜文 Liu Tielong;Qi Wenqiang;Jiang Hongyang;Wang Ruixue;Dai Zhigang;Yin Jiangwen(Dept of Anesthesiology,The First Affiliated Hospital of Shihezi University,Shihezi 832000)

机构地区：[1]石河子大学第一附属医院麻醉科,石河子832000

出　　处：《安徽医科大学学报》2023年第7期1071-1076,共6页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:82160235)。

摘　　要：目的探讨紫草酸甲酯(PAME)对小鼠术后学习记忆障碍的影响及机制。方法将C57BL/6J雄性小鼠随机分为Sham组、手术组、手术+PAME组(PAME组)、手术+NADPH氧化酶4(Nox4)腺相关病毒过表达组(Nox4过表达组)、手术+Nox4腺相关病毒空载组(AAV空载组)、手术+PAME+Nox4过表达组(PN组)。手术模型采用剖腹探查术,PAME(20 mg/kg)给药时间为术后连续灌胃7 d,Nox4腺相关病毒在手术前28 d注射到海马脑区。Morris水迷宫实验和条件性恐惧实验检测小鼠学习记忆能力;免疫荧光观察Nox4表达变化;Western blot法检测Nox4、长链脂酰辅酶A合成酶4(ACSL4)和谷胱甘肽过氧化物酶4(GPX4)表达;分光光度法检测活性氧(ROS)和铁含量。结果与Sham组相比,手术组、Nox4过表达组、AAV空载组小鼠学习记忆能力下降,Nox4、ACSL4表达升高,GPX4表达降低,ROS、铁含量增加,PAME治疗后小鼠术后学习记忆能力改善,海马神经元Nox4和铁死亡减轻。结论PAME治疗后可提高术后小鼠学习记忆能力,与其抑制海马Nox4介导的铁死亡有关。Objective To investigate the effect of paederosidic acid methyl ester(PAME)on postoperative learning and memory impairment in mice and its mechanism.Methods C57BL/6J male mice were randomly divided into Sham group,operation group,operation+PAME group(PAME group),operation+NADPH oxidase 4(Nox4)adeno-associated virus overexpression group(Nox4 overexpression group),operation+Nox4 adeno-associated virus no-laden group(AAV no-load group),and operation+PAME+Nox4 overexpression group(PN group).Exploratory laparotomy was performed.PAME(20 mg/kg)was administered by continuous gavage for 7 days after operation,and adeno-associated virus was injected into the hippocampus 28 days before operation.Morris Water maze test and conditioned fear test were used to detect the learning and memory ability of mice.The expression of Nox4 protein was observed by immunofluorescence.The protein expressions of Nox4,long chain acyl CoA synthetase 4(ACSL4)and glutathione peroxidase 4(GPX4)were detected by Western blot.Reactive oxygen species(ROS)and iron content were determined by spectrophotometry.Results Compared with the Sham group,the learning and memory ability of the operation group,the Nox4 overexpression group and the AAV no-load group decreased,the protein expression of Nox4 and ACSL4 increased,the protein expression of GPX4 decreased,and the ROS and iron content increased.After PAME treatment,the postoperative learning and memory ability of mice was improved,and Nox4 and ferroptosis in hippocampal neurons were alleviated.Conclusion PAME treatment can improve the learning and memory ability of postoperative mice,which may be related to the inhibition of hippocampal Nox4-mediated ferroptosis.

关 键 词：紫草酸甲酯 学习记忆 NADPH氧化酶4 铁死亡 海马 

分 类 号：R964[医药卫生—药理学]