β-羟基丁酸改善β淀粉样蛋白1-42诱导小鼠海马神经元HT22细胞的能量障碍  

Beta-hydroxybutyric acid improves energy dysfunction of mouse hippocampal neuron HT22 cells induced by amyloid-βprotein 1-42

作　　者：叶育采 付朝晶 李燕[2] 李欣儒 柴世凡 蔡红艳 王昭君[1] Ye Yucai;Fu Chaojing;Li Yan;Li Xinru;Chai Shifan;Cai Hongyan;Wang Zhaojun(Department of Physiology,School of Basic Medicine,Shanxi Medical University,Key Laboratory of Cell Physiology,Ministry of Education,Taiyuan 030000,Shanxi Province,China;Academy of Medical Sciences,Shanxi Medical University,Taiyuan 030000,Shanxi Province,China;Department of Microbiology and Immunology,School of Basic Medicine,Shanxi Medical University,Taiyuan 030000,Shanxi Province,China)

机构地区：[1]山西医科大学基础医学院生理学系,细胞生理学教育部重点实验室,山西省太原市030000 [2]山西医科大学医学科学院,山西省太原市030000 [3]山西医科大学基础医学院微生物与免疫学教研室,山西省太原市030000

出　　处：《中国组织工程研究》2025年第13期2713-2719,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金面上项目(82171428),项目负责人:蔡红艳;山西省基础研究自然科学研究面上项目(20210302123306),项目负责人:王昭君。

摘　　要：背景:阿尔茨海默病患者存在严重的脑能量障碍,近年来基于酮体干预的脑能量拯救策略在阿尔茨海默病的治疗中越来越受到重视。目的:探讨β-羟基丁酸能否改善β淀粉样蛋白1-42(β-amyloid protein 1-42,Aβ_(1-42))诱导的小鼠海马神经元HT22细胞能量障碍。方法:将HT22细胞分为4组,分别为对照组、β-羟基丁酸组、Aβ_(1-42)组、Aβ_(1-42)+β-羟基丁酸组。使用相应试剂盒检测HT22细胞的存活率、ATP水平、α-酮戊二酸脱氢酶活性、Na^(+)K^(+)-ATP酶活性、线粒体膜电位及活性氧水平。结果与结论:与对照组相比,Aβ_(1-42)组HT22细胞的存活率、ATP水平、α-酮戊二酸脱氢酶活性、Na^(+)K^(+)-ATP酶活性、线粒体膜电位均显著降低(P<0.05),活性氧水平显著升高(P<0.05)。与Aβ_(1-42)组相比,Aβ_(1-42)+β-羟基丁酸组HT22细胞的存活率、ATP水平、α-酮戊二酸脱氢酶活性、Na^(+)K^(+)-ATP酶活性、线粒体膜电位均显著升高(P<0.05),活性氧水平显著降低(P<0.05)。结果表明:β-羟基丁酸提高了线粒体生物能量功能和细胞存活率,最终改善了Aβ_(1-42)诱导的HT22细胞能量障碍。BACKGROUND:Patients with Alzheimer’s disease have severe brain energy disorders.In recent years,brain energy rescue strategies based on ketone body intervention have attracted more and more attention in the treatment of Alzheimer’s disease.OBJECTIVE:To investigate whetherβ-hydroxybutyric acid can improve energy dysfunction by improving mitochondrial bioenergy function in HT22 cells of mouse hippocampal neurons induced by amyloid-βprotein 1-42(Aβ_(1-42)).METHODS:HT22 cells were divided into four groups:Control,β-hydroxybutyric acid,Aβ_(1-42),Aβ_(1-42)+β-hydroxybutyric acid.Related detection kits were respectively used to detect HT22 cell survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na^(+)K^(+)-ATPase activity,mitochondrial membrane potential,and reactive oxygen species levels.RESULTS AND CONCLUSION:Compared with the control group,the survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na^(+)K^(+)-ATPase activity,and mitochondrial membrane potential of HT22 cells were significantly decreased(P<0.05),and the level of reactive oxygen species was significantly increased(P<0.05)in the Aβ_(1-42) group.Compared with the Aβ_(1-42) group,the survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na^(+)K^(+)-ATPase activity,and mitochondrial membrane potential of HT22 cells were significantly increased(P<0.05),and the reactive oxygen species level was significantly decreased(P<0.05)in the Aβ_(1-42)+β-hydroxybutyric acid group.These results showed thatβ-hydroxybutyric acid improved mitochondrial bioenergetic function and ultimately improved Aβ_(1-42)-induced energy impairment and survival rate in HT22 cells.

关 键 词：阿尔茨海默病 HT22细胞 β-羟基丁酸 线粒体生物能量功能 能量障碍 三磷酸腺苷 

分 类 号：R459.9[医药卫生—治疗学] R338[医药卫生—临床医学] R741