Relationship between decline of exercise ability and mitochondrial damage in skeletal muscle of mice with high-altitude de-acclimatization
10.3969/j.issn.1000-4718.2025.07.014
- VernacularTitle:高原脱习服小鼠运动能力下降与骨骼肌线粒体损伤的关系研究
- Author:
Yehui GAO
1
;
Huiying SHANG
;
Hongbo CHENG
;
Weiye HAN
;
Wei ZHOU
;
Zhiping YU
;
Xianglin TANG
;
Chengrong XIAO
;
Xian LIU
;
Yue GAO
Author Information
1. 天津中医药大学,天津 301617;军事科学院军事医学研究院,北京 100850
- Publication Type:Journal Article
- Keywords:
high-altitude de-acclimatization;
exercise capacity;
skeletal muscle;
oxidative phosphorylation;
mitochondrial production;
mitochondrial fusion
- From:
Chinese Journal of Pathophysiology
2025;41(7):1375-1382
- CountryChina
- Language:Chinese
-
Abstract:
AIM:This study aims to investigate the mechanisms underlying skeletal muscle mitochondrial damage associated with decline in exercise function during high-altitude de-adaptation,using a mouse model.METHODS:Twen-ty-four healthy male C57BL/6J mice were randomly assigned to two groups:a high-altitude de-adaptation group and a plain control group.The model group was exposed to a low-pressure,low-oxygen chamber simulating an altitude of 7 000 meters for two weeks,followed by eight days of rearing in a plain environment.The control group was maintained in a plain envi-ronment for the same duration.Grip strength and pole-climbing tests were conducted on the 1st,3rd,and 5th days post-re-turn to assess muscle strength and motor coordination.Treadmill exercises were performed on the 4th and 8th days to eval-uate exercise endurance.After the treadmill exercise on the 8th day,serum,liver,and skeletal muscle tissues were col-lected.Levels of lactic acid(LA),glucose(GLU),creatine kinase(CK),lactate dehydrogenase(LDH),alanine trans-aminase(ALT),and aspartate aminotransferase(AST)in serum,as well as glycogen levels in the liver and muscle,were analyzed.Additionally,the expression of proteins related to mitochondrial biogenesis,fission,fusion,and oxidative phos-phorylation in muscle tissues was assessed using Western blot.RESULTS:(1)The model group exhibited significant re-ductions in grip strength,increased pole-climbing T-turn and total times,and decreased total time and distance in the ex-haustion running test.(2)Serum levels of LA,CK,LDH,ALT,and AST were elevated,while GLU levels decreased,and glycogen levels in both the liver and muscle were reduced in the model group following the treadmill exercise.(3)Ab-normal indicators in the model group did not return to normal by the end of the de-adaptation period.(4)Western blot analysis revealed decreased expression of mitochondrial oxidative phosphorylation proteins(ATP6V1A and Mt-CO2)and mitochondrial biogenesis proteins(PGC-1α and FGF21),increased levels of mitochondrial fusion proteins(OPA1 and MFN1),and no significant changes in fission protein expression(FIS1 and DRP1)in muscle tissue from the model group.CONCLUSION:Exercise capacity in mice during the high-altitude de-adaptation period significantly declined,particu-larly in terms of muscle strength,motor coordination,and endurance.This decline is closely associated with abnormal pro-tein expression related to skeletal muscle mitochondrial energy metabolism and production.
