Mechanism of intramuscular injection of glycyl-tRNA synthetase in improving denervated muscular atrophy in mice

您当前的位置：

首页 >

文章列表页 >

Mechanism of intramuscular injection of glycyl-tRNA synthetase in improving denervated muscular atrophy in mice

Basic Research | 更新时间：2026-03-09

- Mechanism of intramuscular injection of glycyl-tRNA synthetase in improving denervated muscular atrophy in mice
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 35, Issue 2, Pages: 127-132(2026)
- 作者机构：
  
  1.遵义医科大学人体解剖学教研室，贵州遵义 563000
  2.遵义医科大学2022级第一临床学院，贵州遵义 563000
- 作者简介：
- 基金信息：
- DOI：10.11659/jjssx.02E025007
  CLC： R322
- Received：05 February 2025，
  
  Published：25 February 2026
- 稿件说明：
移动端阅览
王猛,李旭灿,王宇等.甘氨酰-tRNA合成酶肌内注射改善小鼠失神经肌萎缩的机制研究[J].局解手术学杂志,2026,35(02):127-132.

WANG Meng,LI Xu-can,WANG Yu,et al.Mechanism of intramuscular injection of glycyl-tRNA synthetase in improving denervated muscular atrophy in mice[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(02):127-132.
王猛,李旭灿,王宇等.甘氨酰-tRNA合成酶肌内注射改善小鼠失神经肌萎缩的机制研究[J].局解手术学杂志,2026,35(02):127-132. DOI： 10.11659/jjssx.02E025007.

WANG Meng,LI Xu-can,WANG Yu,et al.Mechanism of intramuscular injection of glycyl-tRNA synthetase in improving denervated muscular atrophy in mice[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(02):127-132. DOI： 10.11659/jjssx.02E025007.

摘要

目的

2

探讨甘氨酰-tRNA合成酶（GlyRS）肌内注射改善小鼠失神经肌萎缩的作用机制。

方法

2

构建GlyRS过表达腺病毒载体，进行PCR鉴定和测序。将54只雄性SPF级昆明小鼠随机分为对照（C）组（暴露坐骨神经，但不离断损伤）、坐骨神经离断损伤（SNI）组（构建SNI致胫骨前肌萎缩模型）、SNI+NC组（建模后转染空病毒载体）、SNI+GlyRS组（建模后转染GlyRS过表达腺病毒载体），每组12只，其余6只小鼠胫骨前肌作冰冻切片。荧光显微镜检测GlyRS过表达腺病毒载体转染昆明小鼠胫骨前肌的效果；测量各组小鼠胫骨前肌肌重和肌纤维横截面积。qRT-PCR和Western blot检测各组小鼠胫骨前肌的GlyRS、mTOR的mRNA和蛋白表达水平。

结果

2

GlyRS过表达腺病毒载体经PCR鉴定和测序正确，并成功转染小鼠患侧胫骨前肌。与C组相比，SNI组小鼠胫骨前肌肌重和肌纤维横截面积明显减少（

P

<

0.01），GlyRS和mTOR的mRNA和蛋白表达水平升高（

P

<

0.01）；与SNI组相比，SNI+NC组小鼠胫骨前肌肌重和肌纤维横截面积无显著变化（

P

>

0.05），GlyRS和mTOR的mRNA和蛋白表达水平升高（

P

<

0.01），SNI+GlyRS组小鼠胫骨前肌肌重和肌纤维横截面积明显增加（

P

<

0.01），GlyRS和mTOR的mRNA和蛋白表达水平明显升高（

P

<

0.01）；与SNI+NC组相比，SNI+GlyRS组小鼠胫骨前肌肌重和肌纤维横截面积明显增加（

P

<

0.01），GlyRS和mTOR的mRNA和蛋白表达水平明显升高（

P

<

0.01）。

结论

2

GlyRS肌内注射可能通过促进mTOR的合成改善小鼠坐骨神经离断损伤所致的胫骨前肌萎缩。

Abstract

Objective

2

To investigate the mechanism of intramuscular injection of glycyl tRNA synthetase （GlyRS） in improving denervated muscular atrophy in mice.

Methods

2

GlyRS overexpression adenovirus vector was constructed for PCR identification and sequencing. A total of 54 male SPF Kunming mice were randomly divided into control （C） group （the sciatic nerve was exposed， but not transection injury）， sciatic nerve transection injury（SNI） group （constructing a model of tibialis anterior muscle atrophy induced by SNI）， SNI+NC group （transfected an empty viral vector after modeling）， and SNI+GlyRS group （transfected with GlyRS overexpression adenoviral vector after modeling）， with 12 mice in each group； and the tibialis anterior muscle of the remaining 6 mice were used to make frozen sections. Fluorescence microscope was used to detect the transfection effect of GlyRS overexpression adenovirus vector on tibialis anterior muscle of Kunming mice. Tibialis anterior muscle weight and muscle fiber cross-sectional area of mice in each group were measured. qRT-PCR and Western blot were used to detect the mRNA and protein expression levels of GlyRS and mTOR in tibialis anterior muscle of mice in each group.

Results

2

The GlyRS overexpression adenoviral vector was identified and sequenced correctly by PCR，and successfully transfected into the affected tibialis anterior muscle of mice. Compared with group C， the tibialis anterior muscle weight and muscle fiber cross-sectional area of mice

in SNI group were significantly decreased （

P

<

0.01）， and the mRNA and protein expression levels of GlyRS and mTOR were increased （

P

<

0.01）. Compared with SNI group， the tibialis anterior muscle weight and muscle fiber cross-sectional area of mice in SNI+NC group had no significant changes （

P

>

0.05）， and the mRNA and protein expression levels of GlyRS and mTOR were increased （

P

<

0.01）；the tibialis anterior muscle weight and muscle fiber cross-sectional area of mice in the SNI+GlyRS group were significantly increased （

P

<

0.01）， and the mRNA and protein expression levels of GlyRS and mTOR were significantly increased （

P

<

0.01）. Compared with SNI+NC group， the tibialis anterior muscle weight and muscle fiber cross-sectional area of mice in SNI+GlyRS group were significantly increased （

P

<

0.01）， and the mRNA and protein expression levels of GlyRS and mTOR were significantly increased （

P

<

0.01）.

Conclusion

2

Intramuscular injection of GlyRS may improve tibialis anterior muscle atrophy induced by sciatic nerve transection injury in mice by promoting the synthesis of mTOR.

关键词

Keywords

references

Kubat GB ， Bouhamida E ， Ulger O ， et al . Mitochondrial dysfunction and skeletal muscle atrophy：causes，mechanisms，and treatment strategies ［J］. Mitochondrion ， 2023 ， 72 ： 33 - 58 . doi： 10.1016/j.mito.2023. 07.003 http://dx.doi.org/10.1016/j.mito.2023.07.003 .

Yin L ， Li N ， Jia W ， et al . Skeletal muscle atrophy：from mechanisms to treatments ［J］. Pharmacol Res ， 2021 ， 172 ： 105807 . doi： 10.1016/j.phrs.2021.105807 http://dx.doi.org/10.1016/j.phrs.2021.105807 .

Ito N ， Ruegg UT ， Takeda S . ATP-induced increase in intracellular calcium levels and subsequent activation of mTOR as regulators of skeletal muscle hypertrophy ［J］. Int J Mol Sci ， 2018 ， 19 （ 9 ）： 2804 . doi： 10.3390/ijms19092804 http://dx.doi.org/10.3390/ijms19092804 .

Oprescu SN ， Chepa-Lotrea X ， Takase R ， et al . Compound heterozygosity for loss-of-function GARS variants results in a multisystem developmental syndrome that includes severe growth retardation ［J］. Hum Mutat ， 2017 ， 38 ： 1412 - 1420 . doi： 10.1002/humu.23287 http://dx.doi.org/10.1002/humu.23287 .

Matthew CC ， Michael R ， Mark B ， et al . Conformational sampling of CMT-2D associated GlyRS mutations ［J］. Brain Multiphys ， 2022 ， 3 ： 100054 . doi： 10.1016/j.brain.2022.100054 http://dx.doi.org/10.1016/j.brain.2022.100054 .

Niehues S ， Bussmann J ， Steffes G ， et al . Impaired protein translation in Drosophila models for Charcot-Marie-Tooth neuropathy caused by mutant tRNA synthetases ［J］. Nat Commun ， 2015 ， 3 （ 6 ）： 7520 . doi： 10.1038/ncomms8520 http://dx.doi.org/10.1038/ncomms8520 .

Luo C ， Qi H ， Huang X ， et al . GlyRS is a new mediator of amino acid-induced milk synthesis in bovine mammary epithelial cells ［J］. J Cell Physiol ， 2019 ， 234 （ 3 ）： 2973 - 2983 . doi： 10.1002/jcp.27115 http://dx.doi.org/10.1002/jcp.27115 .

Wang M ， Zhang XM ， Yang SB . Effect of electroacupuncture on the expression of Glycyl-tRNA synthetase and ultrastructure changes in atrophied rat peroneus longus muscle induced by sciatic nerve injection injury ［J］. Evid Based Complement Alternat Med ， 2016 ： 7536234 . doi： 10.1155/2016/7536234 http://dx.doi.org/10.1155/2016/7536234 .

Nikonova EY ， Mihaylina AO ， Nemchinova MS ， et al . Glycyl-tRNA synthetase as a potential universal regulator of translation initiation at IRES-I ［J］. Mol Biol （Mosk）， 2018 ， 52 （ 1 ）： 10 - 18 . doi： 10.7868/S0026 898418010020 http://dx.doi.org/10.7868/S0026898418010020 .

Johanson K ， Hoang T ， Sheth M ， et al . GRS1，a yeast tRNA synthetase with a role in mRNA 3' end formation ［J］. J Biol Chem ， 2003 ， 278 （ 38 ）： 35923 - 35930 . doi： 10.1074/jbc.M304978200 http://dx.doi.org/10.1074/jbc.M304978200 .

Guo RT ， Chong YE ， Guo M ， et al . Crystal structures and biochemical analyses suggest a unique mechanism and role for human glycyl-tRNA synthetase in Ap4A homeostasis ［J］. J Biol Chem ， 2009 ， 284 （ 42 ）： 28968 - 28976 . doi： 10.1074/jbc.M109.030692 http://dx.doi.org/10.1074/jbc.M109.030692 .

Yu M ， Luo C ， Huang X ， et al . Amino acids stimulate glycyl-tRNA synthetase nuclear localization for mammalian target of rapamycin expression in bovine mammary epithelial cells ［J］. J Cell Physiol ， 2019 ， 234 （ 5 ）： 7608 - 7621 . doi： 10.1002/jcp.27523 http://dx.doi.org/10.1002/jcp.27523 .

Yoshida T ， Delafontaine P . Mechanisms of IGF-1-mediated regulation of skeletal muscle hypertrophy and atrophy ［J］. Cells ， 2020 ， 9 （ 9 ）： 1970 . doi： 10.3390/cells9091970 http://dx.doi.org/10.3390/cells9091970 .

Grüner S ， Peter D ， Weber R ， et al . The structures of eIF4E-eIF4G complexes reveal an extended interface to regulate translation initiation ［J］. Mol Cell ， 2016 ， 64 （ 3 ）： 467 - 479 . doi： 10.1016/j.molcel.2016. 09.020 http://dx.doi.org/10.1016/j.molcel.2016.09.020 .

Liu GY ， Sabatini DM . mTOR at the nexus of nutrition，growth，ageing and disease ［J］. Nat Rev Mol Cell Biol ， 2020 ， 21 （ 4 ）： 183 - 203 . doi： 10.1038/s41580-019-0199-y http://dx.doi.org/10.1038/s41580-019-0199-y .

Huang K ， Fingar DC . Growing knowledge of the mTOR signaling network ［J］. Semin Cell Dev Biol ， 2014 ， 36 ： 79 - 90 . doi： 10.1016/j.semcdb.2014.09.011 http://dx.doi.org/10.1016/j.semcdb.2014.09.011 .

吴梦佳，唐成林，黄思琴，等 . 电针对大鼠失神经腓肠肌中哺乳动物雷帕霉素靶蛋白/70KD核糖体蛋白S6激酶信号通路的影响［J］. 中国康复理论与实践， 2018 ， 24 （ 9 ）： 1022 - 1026 . doi： 10.3969/j.issn.1006-9771.2018.09.006 http://dx.doi.org/10.3969/j.issn.1006-9771.2018.09.006 .

Baden LR ， Liu J ， Li H ， et al . Induction of HIV-1-specific mucosal immune responses following intramuscular recombinant adenovirus serotype 26 HIV-1 vaccination of humans ［J］. J Infect Dis ， 2014 ， 211 （ 4 ）： 518 - 528 . doi： 10.1093/infdis/jiu485 http://dx.doi.org/10.1093/infdis/jiu485 .

Bricker TL ， Darling TL ， Hassan AO ， et al . A single intranasal or intramuscular immunization with chimpanzee adenovirus vectored SARS-CoV-2 vaccine protects against pneumonia in hamsters ［J］. Cell Rep ， 2021 ， 36 （ 3 ）： 109400 . doi： 10.1016/j.celrep.2021.109400 http://dx.doi.org/10.1016/j.celrep.2021.109400 .

刘洪文，朱国涛，陈锦成，等 . 失神经骨骼肌萎缩的机制及防治研究进展［J］. 中国临床研究， 2019 ， 32 （ 8 ）： 1116 - 1118 . doi： 10.13429/j.cnki.cjcr.2019.08.029 http://dx.doi.org/10.13429/j.cnki.cjcr.2019.08.029 .

Zheng YX ， Chen XB ， Xu F ， et al . Glycyl-tRNA synthetase induces psoriasis-like skin by facilitating skin inflammation and vascular endothelial cell angiogenesis ［J］. J Invest Dermatol ， 2024 ， 144 （ 4 ）： 774 - 785 . doi： 10.1016/j.jid.2023.09.270 http://dx.doi.org/10.1016/j.jid.2023.09.270 .

Wang JH ， Yang B ， Wang DX ， et al . GARS is implicated in poor survival and immune infiltration of hepatocellular carcinoma ［J］. Cell Signal ， 2022 ， 94 ： 110302 . doi： 10.1016/j.cellsig.2022.110302 http://dx.doi.org/10.1016/j.cellsig.2022.110302 .

Park MC ， Kang T ， Jin D ， et al . Secreted human glycyl-tRNA synthetase implicated in defense against ERK-activated tumorigenesis ［J］. Proc Natl Acad Sci USA ， 2012 ， 109 （ 11 ）： E640 - E647 . doi： 10.1073/pnas.1200194109 http://dx.doi.org/10.1073/pnas.1200194109 .

Mo ZY ， Zhang Q ， Liu Z ， et al . Neddylation requires glycyl-tRNA synthetase to protect activated E2 ［J］. Nat Struct Mol Biol ， 2016 ， 23 ： 730 - 737 . doi： 10.1038/nsmb.3250 http://dx.doi.org/10.1038/nsmb.3250 .

0

Views

4

下载量

0

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Related Articles

Application of the self-made nerve bundle with 3 mm of spatial distance between the two ends in repair of median nerve rupture of the wrist

Neuroprotective effect of Zhenbao pill mediated NF-κB/p65 pathway on rats with spinal cord injury

Related Author

ZHENG Hui

HAO Yi-wei

JIANG Qi-ting

XIE Ling-han

WANG Xing

LI Si-qin

ZHANG Bao-xin

Related Institution

Department of Orthopedics， the Fourth Affiliated Hospital of Nanjing Medical University

Nanjing Jiangbei New District Taishan Street Community Health Service Center

Department of Hand and Foot Microsurgery，Nanjing Jiangbei Hospital

Department of Spine，Bayannur City Hospital

Department of Neurosurgery， Bayannur City Hospital

⁰