Effect of chronic intermittent hypoxia exposure: differences on soleus muscle and musculi tibialis anterior

Pengyu FU; Jie JIA; Lijing GONG

doi:10.16016/j.2097-0927.202108143

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Effect of chronic intermittent hypoxia exposure: differences on soleus muscle and musculi tibialis anterior

Basic Medicine | 更新时间：2026-01-09

- Effect of chronic intermittent hypoxia exposure: differences on soleus muscle and musculi tibialis anterior
- Journal of Army Medical University Vol. 44, Issue 5, Pages: 432-440(2022)
- 作者机构：
  
  1.710072 西安，西北工业大学体育部
  2.100084 北京，北京体育大学：运动人体科学学院
  3.100084 北京，北京体育大学：运动与体质健康教育部重点实验室
- 作者简介：
- 基金信息：
  
  the Fundamental Research Fund for Central Universities of China(D5000210831);the Special Fund for Guiding Central Universities to Build World-Class Universities (Disciplines) and Characteristic Development(21GH031119)
- DOI：10.16016/j.2097-0927.202108143
  CLC： R322.74;R363.22;R364.4
- Received：20 August 2021，
  
  Revised：2021-11-04，
  
  Published：15 March 2022
- 稿件说明：
移动端阅览
Pengyu FU, Jie JIA, Lijing GONG. Effect of chronic intermittent hypoxia exposure: differences on soleus muscle and musculi tibialis anterior[J]. Journal of Army Medical University, 2022, 44(5): 432-440.
DOI：

Pengyu FU, Jie JIA, Lijing GONG. Effect of chronic intermittent hypoxia exposure: differences on soleus muscle and musculi tibialis anterior[J]. Journal of Army Medical University, 2022, 44(5): 432-440. DOI： 10.16016/j.2097-0927.202108143.

摘要

目的

对比慢性间歇性低氧暴露对不同纤维类型肌肉的影响及其可能机制。

方法

SD大鼠16只，分为常氧对照组(C，

=8)，置于常氧环境中；慢性间歇性低氧组(H，

=8)，置于氧浓度为12.4%的低氧房中，每天暴露8 h，共4周。干预期间称量大鼠体质量，干预后测试抓力和瘦体质量，检测比目鱼肌(soleus muscle，SOL)和胫骨前肌(musculi tibialis anterior，TA)湿质量和肌纤维横截面积(muscle fiber cross-sectional area，FCSA)，Western blot检测嘌呤霉素(puromycin，Puro)和泛素(ubiquitin，Ub)的含量，并对SOL和TA进行RNA测序，筛选差异基因，分析差异基因所富集的生物过程和通路。

结果

① 干预期间，C组和H组体质量持续增长，但各时间点H组体质量始终低于C组，干预后H组瘦体质量及其百分比、抓力及相对抓力均低于C组，但差异无统计学意义。②H组TA湿质量较C组显著降低(

0.05)；H组SOL和TA肌纤维均出现损伤；SOL的FCSA显著低于C组(

0.05)。③H组SOL中Puro和Ub均显著高于C组，Puro/Ub显著降低(

0.05)；TA中Puro/Ub显著增加(

0.01)。④两组SOL中差异基因有665个，TA中差异基因有228个，在两种肌肉中均上调的差异基因有58个，均下调的有35个；H/C组SOL中上调差异基因功能主要富集于炎症反应和蛋白合成过程，参与调控的通路为TNF和Jak-STAT信号通路；H/C组TA中上调差异基因功能主要富集于抗氧化、糖代谢和糖皮质激素调控过程，参与调控的通路为PPAR信号通路和谷胱甘肽代谢过程，下调基因富集于快肌和慢肌之间的转化和氧化应激过程。

结论

慢性间歇性低氧可能通过增加炎症反应以促进比目鱼肌萎缩，而胫骨前肌可能通过提高抗氧化能力以抵抗低氧诱导的肌萎缩。

Abstract

Objective

To compare the effects of chronic intermittent hypoxia exposure on different fiber types of muscle and investigate its possible mechanism.

Methods

Sixteen SD rats were randomly divided into normoxia control group (C group

placed in a normoxic chamber) and chronic intermittent hypoxia group (H group

placed in a hypoxic chamber with an oxygen concentration of 12.4%

8 h per day

for 4 weeks). Their body mass was weighed during the intervention

and the grasping force and lean body mass were tested after the intervention. The wet masses of soleus muscle (SOL) and musculi tibialis anterior (TA)

muscle fiber cross-sectional area (FCSA) were measured. The protein levels of puromycin (Puro) and ubiquitin (Ub) were detected with Western blotting. RNA sequencing was carried out for TA tissues to screen the differential genes between the 2 groups. And the biological process and pathways enriched by these differential genes were analyzed.

Results

① During the intervention

the body mass of the C and H groups continued to increase

but it of the H group was always lower than that of the C group at each time point. The intervention also resulted in the decreases in the lean body mass and its percentage

grasping force and relative grasping force in the H group than the C group

but there were no statistical differences. ② The wet mass of TA was significantly lower in the H group than the C group (

0.05). In H group

both SOL and TA muscle fibers were damaged

and the FCSA of SOL was significantly lower than C group (

0.05). ③Puro and Ub in SOL tissues were obviously higher in the H group than the C group. The ratio of Puro/Ub was decreased significantly in SOL tissues (

0.05)

but increased significantly in TA tissues (

0.01). ④ There were 665 differential genes found in SOL tissues and 228 differential genes in TA tissues between the 2 groups. Among them

58 differential genes were up-regulated and 35 were down-regulated in both muscles. Those up-regulated differential genes in SOL tissues were mainly enriched in inflammatory respo

nse and protein synthesis and involved in TNF and Jak/STAT signaling pathways. The up-regulated differential genes in TA tissues were mainly enriched in antioxidant and glucose metabolism and glucocorticoid and involved in PPAR signaling pathway and glutathione metabolism. The down-regulated genes were concentrated in oxidative stress and transformation between fast- and slow-twitch muscles.

Conclusion

Chronic intermittent hypoxia could promote SOL atrophy by enhancing inflammatory response

and TA may resist hypoxia-induced muscle atrophy by improving antioxidant capacity.

关键词

Keywords

references

AUSÍN P, MARTÍNEZ-LLORENS J, SABATÉ-BRESCO M, et al . Sex differences in function and structure of the quadriceps muscle in chronic obstructive pulmonary disease patients[J ] . Chron Respir Dis, 2017, 14(2): 127-139. DOI: 10.1177/1479972316674412.

PAN L L, KE J Q, ZHAO C C, et al . Electrical stimulation improves rat muscle dysfunction caused by chronic intermittent hypoxia-hypercapnia via regulation of miRNA-related signaling pathways[J ] . PLoS One, 2016, 11(3): e0152525. DOI: 10.1371/journal.pone.0152525.

付鹏宇, 胡扬, 龚丽景. 低氧暴露诱导肌萎缩发生的机制探讨[J]. 生理科学进展, 2019, 50(3): 205-210. DOI: 10.3969/j.issn.0559-7765.2019.03.010.

FU P Y, HU Y, GONG L J. Mechanism of myoatrophy induced by hypoxic exposure[J]. Prog Physiol Sci, 2019, 50(3): 205-210. DOI: 10.3969/j.issn.0559-7765.2019.03.010.

杨亚辉, 李健, 李培君, 等. 氧化应激在慢性阻塞性肺疾病骨骼肌功能障碍的作用及运动干预的影响[J]. 中国康复医学杂志, 2021, 36(5): 620-625. DOI: 10.3969/j.issn.1001-1242.2021.05.022.

YANG Y H, LI J, LI P J, et al . Effect of oxidative stress on skeletal muscle dysfunction in chronic obstructive pulmonary disease and effect of exercise intervention[J ] . Chin J Rehabilit Med, 2021, 36(5): 620-625. DOI: 10.3969/j.issn.1001-1242.2021.05.022.

胡扬. 高原训练的多元化发展: 从HiHi到HiLo再到HiHi+ HiHiLo[J]. 体育科学, 2010, 30(11): 74-78. DOI: 10.16469/j.css.2010.11.010.

HU Y. Diversified development of altitude training—from HiHi to HiLo as well as HiHi+HiLo[J]. China Sport Sci, 2010, 30(11): 74-78. DOI: 10.16469/j.css.2010.11.010.

BIGARD A X, BRUNET A, GUEZENNEC C Y, et al . Skeletal muscle changes after endurance training at h igh altitude[J ] . J Appl Physiol, 1991, 71(6): 2114-2121. DOI: 10.1152/jappl.1991.71.6.2114.

付鹏宇, 于加倍, 朱镕鑫, 等. 4周抗阻训练缓解低氧诱导大鼠肌萎缩中不同肌纤维类型的敏感性差异[J]. 环境与职业医学, 2021, 38(8): 901-909. DOI: 10.13213/j.cnki.jeom.2021.21016.

FU P Y, YU J B, ZHU R X, et al . Differential sensitivity of muscle fiber types to hypoxia-induced muscle atrophy in rats relieved by 4-week resistance training[J ] . J Environ Occup Med, 2021, 38(8): 901-909. DOI: 10.13213/j.cnki.jeom.2021.21016.

CHAILLOU T. Skeletal muscle fiber type in hypoxia: adaptation to high-altitude exposure and under conditions of pathological hypoxia[J]. Front Physiol, 2018, 9: 1450. DOI: 10.3389/fphys.2018.01450.

于加倍, 胡扬, 李燕春, 等. 4周爬梯抗阻训练对低氧诱导大鼠骨骼肌萎缩的影响[J]. 中国实验动物学报, 2018, 26(4): 448-453. DOI: 10.3969/j.issn.1005-4847.2018.04.007.

YU J B, HU Y, LI Y C, et al . Effects of 4-week resistance training on hypoxia-induced skeletal muscle atrophy in rats[J ] . Acta Lab Animalis Sci Sin, 2018, 26(4): 448-453. DOI: 10.3969/j.issn.1005-4847.2018.04.007.

龚丽景, 付鹏宇, 朱镕鑫, 等. 低氧对肥胖小鼠棕色脂肪组织相关基因表达的影响及其机制[J]. 中国应用生理学杂志, 2018, 34(1): 88-92, 100. DOI: 10.12047/j.cjap.5507.2018.022.

GONG L J, FU P Y, ZHU R X, et al . Effects and mechanism of hypoxia exposure on related genes in brown fat tissue of obese mice based on mRNA expression profile microarray[J ] . Chin J Appl Physiol, 2018, 34(1): 88-92, 100. DOI: 10.12047/j.cjap.5507.2018.022.

CHAILLOU T, KOULMANN N, MEUNIER A, et al . Effect of hypoxia exposure on the recovery of skeletal muscle phenotype during regeneration[J ] . Mol Cell Biochem, 2014, 390(1/2): 31-40. DOI: 10.1007/s11010-013-1952-8.

CHAUDHARY P, SHARMA Y K, SHARMA S, et al . High altitude mediated skeletal muscle atrophy: Protective role of curcumin[J ] . Biochimie, 2019, 156(1): 138-147. DOI: 10.1016/j.biochi.2018.10.012.

UOZUMI N, MATSUMOTO H, SAITOH H. Detection of O-propargyl-puromycin with SUMO and ubiquitin by click chemistry at PML-nuclear bodies during abortive proteasome activities[J]. Biochem Biophys Res Commun, 2016, 474(2): 247-251. DOI: 10.1016/j.bbrc.2016.03.155.

SANDRI M, SANDRI C, GILBERT A, et al . Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy[J ] . Cell, 2004, 117(3): 399-412. DOI: 10.1016/s0092-8674(04)00400-3.

CHENG W J, LIU X, ZHANG L, et al . Chronic intermittent hypobaric hypoxia attenuates skeletal muscle ischemia-reperfusion injury in mice[J ] . Life Sci, 2019, 231(8): 116533. DOI: 10.1016/j.lfs.2019.06.008.

LI J, YI X, YAO Z, et al . TNF receptor-associated factor 6 mediates TNFα-induced skeletal muscle atrophy in mice during aging[J ] . J Bone Mine Res, 2020, 35(8): 1535-1548. DOI: 10.1002/jbmr.4021.

PASSMORE L A, BARFORD D. Getting into position: the catalytic mechanisms of protein ubiquitylation[J]. Biochem J, 2004, 379(pt 3): 513-525. DOI: 10.1042/bj20040198.

桑亚洲, 张艳, 陈玉龙, 等. JAK/STAT3介导肿瘤恶病质肌肉萎缩及药物干预研究进展[J]. 中国比较医学杂志, 2021, 31(7): 118-124. DOI: 10.3969/j.issn.1671-7856.2021.07.018.

SANG Y Z, ZHANG Y, CHEN Y L, et al . JAK/STAT3 mediated muscle atrophy in cancer Cachexia and drug intervention[J ] . Chin J Comp Med, 2021, 31(7): 118-124. DOI: 10.3969/j.issn.1671-7856.2021.07.018.

RYAN S. Adipose tissue inflammation by intermittent hypoxia: mechanistic link between obstructive sleep apnoea and metabolic dysfunction[J]. J Physiol, 2017, 595(8): 2423-2430. DOI: 10.1113/jp273312.

黄蓓, 刘隆福, 蒋铁建. 糖皮质激素与肌少症[J]. 中华骨质疏松和骨矿盐疾病杂志, 2020, 13(5): 486-492. DOI: 10.3969/j.issn.1674-2591.2020.05.014.

HUANG B, LIU L F, JIANG T J. Glucocorticoid and sarcopenia[J]. Chin J Osteoporos Bone Miner Res, 2020, 13(5): 486-492. DOI: 10.3969/j.issn.1674-2591.2020.05.014.

YANG Y, LIAO Z, XIAO Q. Metformin ameliorates skeletal muscle atrophy in Grx1 KO mice by regulating intramuscular lipid accumulation and glucose utilization[J]. Biochem Biophys Res Commun, 2020, 533(4): 1226-1232. DOI: 10.1016/j.bbrc.2020.09.119.

DAI J X, XIANG Y X, FU D, et al . Ficus carica L. attenuates denervated skeletal muscle atrophy via PPARα/NF-κB pathway[J ] . Front Physiol, 2020, 11: 580223. DOI: 10.3389/fphys.2020.580223.

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