首页|基于核磁共振技术探究急性肝损伤伴认知功能障碍小鼠不同脑区代谢物变化

基于核磁共振技术探究急性肝损伤伴认知功能障碍小鼠不同脑区代谢物变化

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目的 观察急性肝损伤伴认知功能障碍小鼠不同脑区代谢物变化.方法 将28只雄性C57BL/6小鼠采用随机数法分为对照组(8只)和急性肝损伤组(ALI组,20只),ALI组小鼠在注射硫代乙酰胺诱导急性肝损伤后,通过对行为学结果的层次聚类分析将其分为ALI伴认知功能障碍组(CD组)和ALI不伴认知功能障碍组(非CD组)小鼠.1 H-核磁共振(1 H-NMR)检测CD组小鼠不同脑区代谢物变化.组间比较采用独立样本t检验.结果 有55%(11/20)的小鼠发生认知功能障碍,CD组和非CD组均表现出相似的肝损伤.非CD组在Y-maze新臂的探索时间高于CD组[(111.54±19.32)s 比(63.96±14.59)s,t=6.28,P<0.01].对照组与 CD 组相比,额叶皮层γ-氨基丁酸合成减少 25.08%(0.78/3.11)[(3.11±0.34)μmol/g 比(2.33±0.26)μmol/g,t=5.35,P<0.05],海马和额叶皮层乳酸减少 32.50%(1.82/5.60)、38.98%(2.90/7.44)[(5.60±0.35)μmol/g 比(3.78±0.75)μmol/g,t=5.98,P<0.05;(7.44±0.77)μmol/g 比(4.54±0.89)μmol/g,t=6.98,P<0.05];乙酰天门冬氨酸减少32.12%(1.24/3.86)、32.74%(1.46/4.46)[(3.86±0.35)μmol/g 比(2.62±0.54)µmol/g,t=5.34,P<0.05;(4.46±0.18)μmol/g 比(3.00±0.54)μmol/g,t=6.98,P<0.05];牛磺酸减少 34.15%(6.72/19.68)、26.49%(5.65/21.33)[(19.68±1.69)μmol/g 比(12.96±2.43)μmol/g,t=6.32,P<0.05;(21.33±0.78)μmol/g 比(15.68±2.10)μmol/g,t=6.80,P<0.05].结论 海马和前额叶皮层的神经递质代谢紊乱可能导致急性肝损伤相关的认知功能障碍.
Changes of cerebral metabolites in acute liver injury mice with cognitive dysfunction based on 1H-nuclear magnetic resonance
Objective To investigate the changes in the various metabolites at different brain regions in acute liver injury(ALI)mice with cognitive dysfunction(CD).Methods Totally,28 male C57BL/6 mice were randomly assigned to control(8 mice)and ALI(20 mice)groups.Mice that received thioacetamide(TTA)were classified into ALI mice with or without CD-like phenotypes by hierarchical clus-ter analysis of behavior.1 H-nuclear magnetic resonance(1 H-NMR)was used to detect the changes in vari-ous metabolites at different brain regions in ALI mice with CD.The data were analyzed using two independ-ent sample t-test.Results Approximately 55%(11/20)of mice developed CD.Both CD and non-CD groups manifested identical liver injury.Non-CD group spent more time in the novel arm[(111.54±19.32)s vs.(63.96±14.59)s,t=6.28,P<0.01].Compared to control group,GABA was decreased by 25.08%(0.78/3.11)in the frontal cortex[(3.11±0.34)μmol/g vs.(2.33±0.26)μmol/g,t=5.35,P<0.05],and Lac was decreased by 32.50%(1.82/5.60)and 38.98%(2.90/7.44)[(5.60±0.35)vs.(3.78±0.75)μmol/g,t=5.98,P<0.05;(7.44±0.77)vs.(4.54±0.89)μmol/g,t=6.98,P<0.05],NAA was decreased by 32.12%(1.24/3.86)and 32.74%(1.46/4.46)[(3.86±0.35)vs.(2.62±0.54)μmol/g,t=5.34,P<0.05;(4.46±0.18)vs.(3.00±0.54)μmol/g,t=6.98,P<0.05],and Tau was decreased by 34.15%(6.72/19.68)and 26.49%(5.65/21.33)[(19.68±1.69)vs.(12.96±2.43)μmol/g,t=6.32,P<0.05;(21.33±0.78)vs.(15.68±2.10)μmol/g,t=6.80,P<0.05]in hippocampus and frontal cortex in the CD group.Conclusion Cerebral neurotransmitter metabolism dysfunction in the frontal cortex and the hippocampus may contribute to ALI-associated CD.

Acute liver injuryMetabolicCognitive dysfunctionHippocampalFrontal cortex

陈英勒、李顺元、王乾、孙天宁、项红兵、刘成

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福建医科大学附属泉州第一医院麻醉科,泉州 362002

华中科技大学同济医学院附属同济医院麻醉学教研室,武汉 430030

急性肝损伤 认知功能障碍 代谢物 海马 前额叶皮层

泉州市科技计划

2021N074S

2024

中华实验外科杂志
中华医学会

中华实验外科杂志

CSTPCD
影响因子:0.759
ISSN:1001-9030
年,卷(期):2024.41(6)