摘要
目的探讨4周高强度间歇训练(high-intensity interval training,HIIT)调节慢性不可预知温和应激(chronic unpredictable mild stress,CUMS)大鼠海马组织中丙酮酸-乳酸轴代谢稳态改善其抑郁样行为的作用机制。方法48只SPF级8周龄雄性SD大鼠随机分为4组:正常安静组(C)、CUMS安静组(M)、正常运动组(HC)和CUMS运动组(HM)。M组与HM组接受8周CUMS造模;HC组与HM组从第5周开始接受4周HIIT干预(3 min(85%~90%)S_(max)+1 min(50%~55%)S_(max),循环3~5次,S_(max)为最大运动速度)。检测HC组与HM组在第4周安静状态下和运动后第0、2、4、8、12、24 h以及各组第8周安静状态下的血乳酸浓度;在第4周末和第8周末,采用糖水偏爱率、旷场实验直立次数与穿越格数等行为学指标评估各组大鼠抑郁样行为。在第8周末行为学测试后采集海马组织,分别采用液质色谱-质谱法(LC-MS)非靶向代谢组学技术、靶标定量技术、酶联免疫吸附分析(ELISA)和蛋白质印迹法(Western blot)检测其代谢物含量、乳酸与丙酮酸浓度、丙酮酸-乳酸轴关键代谢酶含量和单羧酸转运载体(monocarboxylate transporter,MCTs)的蛋白质表达水平。结果4周HIIT干预显著提高了CUMS大鼠糖水偏爱率、旷场实验直立次数和穿越格数;非靶向代谢组学检测发现,与C组相比,M组有21种代谢物发生显著变化,4周HIIT干预后,与C组相比,HC组有14种差异代谢物得到显著回调,与M组相比,HM组有11种差异代谢物得到显著回调;靶标定量结果显示,相比于C组,M组海马组织中乳酸浓度显著降低,丙酮酸浓度显著增加,4周HIIT干预显著增加HM组海马组织中乳酸、丙酮酸浓度,血乳酸浓度变化趋势与海马组织乳酸浓度变化一致,与C组相比,M组LDHB含量显著升高,PKM2和PDH含量以及MCT2与MCT4的蛋白质表达水平显著降低,4周HIIT干预上调了HM组PKM2和PDH含量以及MCT2与MCT4蛋白质表达水平。结论4周HIIT干预可以上调CUMS大鼠的血乳酸浓度以及海马组织中PKM2与PDH代谢酶含量,并上调MCT2与MCT4转运载体蛋白的表达,促进中枢乳酸的摄取与利用,从而调节丙酮酸-乳酸轴的代谢稳态,改善抑郁样行为。
Objective To investigate the role of 4-week high-intensity interval training(HIIT)in modulating the metabolic homeostasis of the pyruvate-lactate axis in the hippocampus of rats with chronic unpredictable mild stress(CUMS)to improve their depressive-like behavior.Methods Forty-eight SPF-grade 8-week-old male SD rats were randomly divided into 4 groups:the normal quiet group(C),the CUMS quiet group(M),the normal exercise group(HC),and the CUMS exercise group(HM).The M and HM groups received 8 weeks of CUMS modeling,while the HC and HM groups were exposed to 4 weeks of HIIT starting from the 5th week(3 min(85%-90%)S_(max)+1 min(50%-55%)S_(max),3-5 cycles,S_(max) is the maximum movement speed).A lactate analyzer was used to detect the blood lactate concentration in the quiet state of rats in the HC and HM groups at week 4 and in the 0,2,4,8,12,and 24 h after exercise,as well as in the quiet state of rats in each group at week 8.Behavioral indexes such as sucrose preference rate,number of times of uprightness and number of traversing frames in the absenteeism experiment,and other behavioral indexes were used to assess the depressive-like behavior of the rats at week 4 and week 8.The rats were anesthetized on the next day after the behavioral test in week 8,and hippocampal tissues were taken for assay.LC-MS non-targeted metabolomics,target quantification,ELISA and Western blot were used to detect the changes in metabolite content,lactate and pyruvate concentration,the content of key metabolic enzymes in the pyruvate-lactate axis,and the protein expression levels of monocarboxylate transporters(MCTs).Results 4-week HIIT intervention significantly increased the sucrose preference rate,the number of uprights and the number of traversed frames in the absent field experiment in CUMS rats;non-targeted metabolomics assay found that 21 metabolites were significantly changed in group M compared to group C,and 14 and 11 differential metabolites were significantly dialed back in the HC and HM groups,respectively,after the 4-week HIIT intervention;the quantitative results of the targeting showed that,compared to group C,lactate concentration in the hippocampal tissues of M group,compared with group C,lactate concentration in hippocampal tissue was significantly reduced and pyruvate concentration was significantly increased,and 4-week HIIT intervention significantly increased the concentration of lactate and pyruvate in hippocampal tissue of HM group;the trend of changes in blood lactate concentration was consistent with the change in lactate concentration in hippocampal tissue;compared with group C,the LDHB content of group M was significantly increased,the content of PKM2 and PDH,as well as the protein expression level of MCT2 and MCT4 were significantly reduced.The 4-week HIIT intervention upregulated the PKM2 and PDH content as well as the protein expression levels of MCT2 and MCT4 in the HM group.Conclusion The 4-week HIIT intervention upregulated blood lactate concentration and PKM2 and PDH metabolizing enzymes in hippocampal tissues of CUMS rats,and upregulated the expression of MCT2 and MCT4 transport carrier proteins to promote central lactate uptake and utilization,which regulated metabolic homeostasis of the pyruvate-lactate axis and improved depressive-like behaviors.
作者
韩雨梅
包春辉
张子威
梁家任
向欢
田俊生
周石
吴爽爽
HAN Yu-Mei;BAO Chun-Hui;ZHANG Zi-Wei;LIANG Jia-Ren;XIANG Huan;TIAN Jun-Sheng;ZHOU Shi;WU Shuang-Shuang(School of Physical Education,Shanxi University,Taiyuan 030006,China;Modern Research Center of Traditional Chinese Medicine,Shanxi University,Taiyuan 030006,China;Faculty of Health,Southern Cross University,NSW 2480,Australia;Shanxi Institute of Sports Science,Taiyuan 030006,China)
出处
《生物化学与生物物理进展》
北大核心
2025年第6期1468-1483,共16页
Progress In Biochemistry and Biophysics
基金
国家自然科学基金(82374153)
山西省基础研究计划(202103021224027)
2023年山西省研究生科研创新项目(2023KY078)资助。
关键词
高强度间歇训练
丙酮酸-乳酸轴
抑郁症
慢性不可预知温和应激
单羧酸转运体
high-intensity interval training
pyruvate-lactate axis
depression
chronic unpredictable mild stress
monocarboxylic acid transporter
