γ-亚麻酸通过下调氧化应激反应抑制NLRP3介导的焦亡并改善脑梗塞小鼠认知障碍  

γ-linolenic Acid Improves Cognitive Impairment in Mice with Cerebral Infarction by Down-Regulating Oxidative Stress Response and Inhibiting NLRP3-Mediated Pyroptosis

作　　者：石剑[1] 贡丽雅 王燕[1] SHI Jian;GONG Liya;WANG Yan(The Second Hospital of Hebei Medical University,Hebei Shijiazhuang 050000,China)

机构地区：[1]河北医科大学第二医院营养科,河北石家庄050000

出　　处：《河北医学》2024年第6期931-936,共6页Hebei Medicine

基　　金：河北省2020年度医学科学研究课题计划,(编号:20200953)。

摘　　要：目的:探究γ-亚麻酸(GLA)对脑梗塞小鼠认知障碍的影响及机制。方法:选取18只雄性小鼠,分为对照组6只、模型组6只和GLA组6只,对模型组以及GLA组以大脑中动脉闭塞术进行脑栓塞小鼠认知障碍模型制作,对照组进行假手术,即手术过程相同但不插入线栓。对照组和模型组每日以1mg/kg生理盐水灌胃,GLA组每日以1mg/kg GLA灌胃14d。以Morris水迷宫评估小鼠的认知障碍情况。处死小鼠并取小鼠大脑组织,以HE染色观察小鼠脑梗死面积,以TUNEL染色观察小鼠神经元凋亡情况,以Western Blot实验检测小鼠海马体中P22、P47、NLRP3、IL-1β、GSDMD以及Caspase-1蛋白表达水平。结果:模型组小鼠的逃逸潜伏期短于GLA组以及对照组,GLA组则短于对照组,模型组的穿越环次数最多,GLA组次之,对照组最少;模型组大脑梗死面积以及神经元凋亡数目最多,GLA组次之,对照组大脑无梗死且无神经元凋亡;模型组P22、P47、NLRP3、IL-1β、GSDMD以及Caspase-1蛋白表达高于GLA组和对照组,GLA组的蛋白表达水平则高于对照组。结论:GLA通过下调氧化应激反应抑制NLRP3介导的焦亡并改善脑梗塞导致的小鼠认知障碍。Objective:To investigate the effect and mechanism ofγ-linolenic acid(GLA)on cognitive impairment in mice with cerebral ischemia.Methods:Eighteen male mice were randomly divided into three groups:control group(n=6),model group(n=6),and GLA group(n=6).The cerebral infarction model was established in the model group and GLA group by middle cerebral artery occlusion(MCAO),and sham surgery was performed in the control group.Mice in the control and model groups were administered saline(1 mg/kg)by gavage daily,while mice in the GLA group were administered GLA(1 mg/kg)by gavage daily for 14 days.Morris water maze test was used to evaluate the cognitive impairment of mice.The infarct area and neuronal apoptosis in the brain tissues were measurd by HE staining and TUNEL staining,respectively.The expression levels of P22,P47,NLRP3,IL-1β,GSDMD,and Caspase-1 proteins in the hippocampus of mice were detected by Western blot.Results:The escape latency and crossing number of mice in the model group were shorter and more than those in the GLA group and control group,respectively.The infarct area and the number of apoptotic neurons in the brain tissues of the model group were the largest,followed by the GLA group,and there was no cerebral infarction or neuronal apoptosis in the control group.The expression levels of P22,P47,NLRP3,IL-1β,GSDMD,and Caspase-1 proteins in the model group were higher than those in the GLA group and control group,while those in the GLA group were higher than those in the control group.Conclusion:GLA improves cognitive impairment in mice with cerebral ischemia by down-regulating oxidative stress and inhibiting NLRP3-mediated pyroptosis.

关 键 词：Γ-亚麻酸 氧化应激 NLRP3 脑梗塞 认知障碍 

分 类 号：R749.1[医药卫生—神经病学与精神病学] R743.3[医药卫生—临床医学]