运动锻炼对创伤后应激障碍小鼠铁死亡相关分子表达的影响  

The effects of exercise on the expression of ferroptosis-related proteins in mice with post-traumatic stress disorder

作　　者：龚晓康 邓荣华[2] 曹心怡 王瑶 倪志粤 赵婉静 肖一帆 GONG Xiaokang;DENG Ronghua;CAO Xinyi;WANG Yao;NI Zhiyue;ZHAO Wanjing;XIAO Yifan(Institutes of Biomedical Sciences,School of Medicine;Department of Pathology and Pathophysiology,School of Medicine,Jianghan University,Wuhan 430056 China)

机构地区：[1]江汉大学武汉生物医学研究院,武汉430056 [2]江汉大学医学部基础医学病理学和病理生理学教研室,武汉430056

出　　处：《神经解剖学杂志》2023年第6期657-664,共8页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(82001281);江汉大学校级科研项目(2022XKZX28);江汉大学学生科研项目(2021Bczd001)。

摘　　要：目的:通过多次连续足底电击制备创伤后应激障碍(PTSD)模型小鼠,观察运动对PTSD小鼠铁死亡相关分子表达的影响以及可能的机制。方法:将35只8周龄C57BL/6J雄性小鼠随机分为正常对照组(Control)、创伤性应激障碍组(PTSD)以及运动组(Exe+PTSD),利用足底电击方法制备小鼠PTSD模型;采用条件恐惧试验箱测试各组小鼠的PTSD样行为;利用铁离子染色检测各组小鼠脑组织中三价铁离子累积情况;利用Western Blot检测各组小鼠脑组织中铁死亡相关分子的表达水平。结果:与Control组相比,PTSD组小鼠在条件恐惧试验箱中僵直时间显著增加(P<0.05),皮质和海马区三价铁离子染色面积显著增加(P<0.05),铁转运蛋白1(FPN1)、谷胱甘肽过氧化酶4(GPX4)和脑源性神经营养因子(BDNF)表达显著降低(P<0.05),而铁死亡下游炎症相关的高迁移率族蛋白B1(HMGB1)表达则显著升高(P<0.05)。与PTSD组相比,Exe+PTSD组小鼠在条件恐惧试验箱僵直时间显著减少(P<0.05),皮质和海马三价铁离子累积显著减少(P<0.05),FPN1、GPX4、BDNF蛋白表达显著上升(P<0.05),HMGB1蛋白表达则显著降低(P<0.05)。结论:PTSD会导致小鼠大脑中铁死亡相关信号通路的活化,而运动锻炼则能够抑制PTSD诱发的铁累积并逆转PTSD诱发的铁死亡相关分子蛋白的异常表达,从而缓解小鼠PTSD样行为。Objective:The study aimed to investigate the effects of exercise on the expression of ferroptosis-related proteins and the associated mechanisms in a post-traumatic stress disorder(PTSD)model induced by transient foot shock.Methods:Thirty-five male C57BL/6J mice(8 weeks old)were randomly divided into three groups:Control group,PTSD group,and Exe+PTSD group.PTSD model mice were established by foot-shock and PTSD behaviors were assessed using a fear conditioning box.Iron distribution areas were detected by Fe 3+staining.Western Blot analysis were performed to determine the expression level of ferroptosis-related proteins in the mice.Results:Compared to the control group,the freezing time and Fe 3+distribution areas in the cortex and hippocampus were significantly increased in the mice with PTSD(P<0.05).The levels of ferroportin1(FPN1),glutathione peroxidase 4(GPX4),and brain-derived neurotrophic factor(BDNF)proteins were significantly decreased(P<0.05),while the expression of high mobility group box 1(HMGB1)protein was significantly elevated(P<0.05).Exercise significantly reduced freezing time and Fe 3+accumulation in the cortex and hippocampus(P<0.05),and it also up-regulated the expression of FPN1,GPX4,and BDNF proteins(P<0.05),while down-regulating HMGB1 expression compared to the PTSD group(P<0.05).Conclusion:This study demonstrates that PTSD induces the ferroptosis-related pathway in mice,and exercise can inhibit iron accumulation and reverse the expression of ferroptosis-related proteins induced by PTSD,thereby alleviating PTSD-like behavior in mice.

关 键 词：创伤后应激障碍 足底电击 铁死亡 运动锻炼 小鼠 

分 类 号：R749.5[医药卫生—神经病学与精神病学]