Mdivi-1通过修复黑质网状部线粒体改善肝性脑病小鼠运动功能  

Mdivi-1 improves motor function of mice with hepatic encephalopathy by repairing mitochondrion in substantia nigra reticulata

作　　者：铁静静 李晓东 倪子薇 黄鑫 吴菲菲 王璐[1] 杨雁灵 王亚云 TIE Jingjing;LI Xiaodong;NI Ziwei;HUANG Xin;WU Feifei;WANG Lu;YANG Yanling;WANG Yayun(Department of Human Anatomy and Histology,School of Medicine,Yan’an University,Yan’an 716000;Department of Hepatobiliary,Pancreatic and Spleen Surgery,the First Affiliated Hospital of Air Force Medical University,Xi’an 710032;Department of Neurobiology,School of Medicine,Yan’an University,Yan’an 716000;Department of Hepatobiliary and Pancreatic Surgery,Affiliated Hospital of Yan’an University,Yan’an 716000;Laboratory of Mitochondrial Plasticity of Nervous System Diseases,National Experimental Teaching Demonstration Center of Basic Medical Science,School of Basic Medicine,Air Force Medical University,Xi’an 710032,China)

机构地区：[1]延安大学医学院人体解剖与组织胚胎学教研室,延安716000 [2]空军军医大学第一附属医院肝胆胰脾外科,西安710032 [3]延安大学医学院神经生物学教研室,延安716000 [4]延安大学附属医院肝胆胰外科,延安716000 [5]空军军医大学基础医学院,神经系统疾病线粒体可塑性实验室,国家级基础医学实验教学示范中心,西安710032

出　　处：《神经解剖学杂志》2024年第4期413-420,共8页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(81870415,82201627);陕西省自然科学基础研究计划重点项目(2022JQ-820)。

摘　　要：目的:探讨急性肝性脑病(AHE)模型小鼠中黑质网状部(SNr)的线粒体变化,以及线粒体分裂抑制剂Mdivi-1对AHE小鼠运动功能和SNr线粒体功能的影响。方法:使用硫代乙酰胺(TAA)腹腔注射构建小鼠的AHE模型并通过腹腔注射给予Mdivi-1处理,利用生化检测试剂盒检测小鼠血清天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)和血氨的变化,并进行旷场实验、转棒疲劳实验以及高架十字迷宫实验观察AHE小鼠的运动功能;电镜下观察SNr的线粒体结构变化,商品化试剂盒检测SNr的线粒体膜电位(MMP)以及细胞的活性氧(ROS)和ATP水平。结果:与对照组相比,AHE小鼠血清中的AST、ALT和血氨含量均增加;小鼠在旷场中的总运动距离减少,转棒疲劳实验以及高架十字迷宫实验中的运动时间均缩短;SNr的线粒体变小变圆、线粒体分裂增加,MMP降低,细胞ROS增加,ATP产生减少。使用Mdivi-1干预后,AHE小鼠血清中的AST、ALT和血氨含量均降低;小鼠在旷场中的总运动距离增加,转棒疲劳实验以及高架十字迷宫实验的运动时间均增多,SNr的线粒体变大、圆率降低,线粒体分裂减少,MMP增加,细胞ROS降低,ATP产生增多。结论:Mdivi-1可以通过修复AHE小鼠SNr的线粒体从而改善运动功能。Objective:To investigate the changes of mitochondria in the substantia nigra pars reticulata(SNr)in a mouse model of acute hepatic encephalopathy(AHE),and the effects of mitochondrial division inhibitor Mdivi-1 on the motor function and mitochondrial function of SNr in AHE mice.Methods:The mouse model of AHE was established by intraperitoneal injection of thioacetamide(TAA)and treated with Mdivi-1.The changes of serum aspartate aminotransferase(AST),alanine aminotransferase(ALT),and blood ammonia were detected by biochemical detection kits.Open field test,rotor-rod fatigue test and elevated plus maze test were performed to observe the motor function of AHE mice.Mitochondrial membrane potential(MMP),cellular reactive oxygen species(ROS)and ATP of SNr were detected by commercial kits.Results:Compared with the control group,the levels of AST,ALT and blood ammonia in AHE mice were increased.The total movement distance of the mice in the open field was reduced,and the movement time of the rotor-rod fatigue test and the elevated plus maze test were shortened.In SNr,mitochondria became smaller and rounder,mitochondrial fission increased,MMP decreased,cellular ROS increased,and ATP production decreased.After treatment with Mdivi-1,the levels of AST,ALT and blood ammonia in AHE mice were decreased.In the open field,the total movement distance of mice increased,the movement time of rotorrod fatigue test and elevated plus maze test increased,the mitochondria of SNr were larger,with decreased roundness,decreased mitochondrial division,increased MMP,decreased cellular ROS,and increased ATP production.Conclusion:Mdivi-1 can improve movement disorders in AHE mice by repairing mitochondrial in the SNr.

关 键 词：急性肝性脑病 黑质网状部 线粒体 Mdivi-1 小鼠 

分 类 号：R575.3[医药卫生—消化系统]