高级检索
中华创伤骨科杂志
期刊首页
过刊列表
高级检索
稿件发表
• 下肢骨折诊治的前沿问题 •
ENGLISH ABSTRACT
交感神经参与调控骨骼肌废用性萎缩的初步探究
程栋梁
张明铭
刘江
沈俊民
王中奇
孙新宇
王端阳
常非凡
张皓博
付品聪
陈铭
李毅
尹鹏滨
张里程
唐佩福
作者及单位信息
·
DOI： 10.3760/cma.j.cn115530-20250103-00004
Involvement of sympathetic nerve in the regulation of disuse atrophy of skeletal muscles: a preliminary study
Cheng Dongliang
Zhang Mingming
Liu Jiang
Shen Junmin
Wang Zhongqi
Sun Xinyu
Wang Duanyang
Chang Feifan
Zhang Haobo
Fu Pincong
Chen Ming
Li Yi
Yin Pengbin
Zhang Licheng
Tang Peifu
Authors Info & Affiliations
Cheng Dongliang
Department of Orthopedic Surgery, The Fourth Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Musculoskeletal and Sports Medicine, Beijing 100048, China
Zhang Mingming
Department of Orthopedic Surgery, The Fourth Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Musculoskeletal and Sports Medicine, Beijing 100048, China
Liu Jiang
Department of Orthopaedic Surgery, The Second Hospital Affiliated to Harbin Medical University, Harbin 150001, China
Shen Junmin
Department of Orthopedic Surgery, The Fourth Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Musculoskeletal and Sports Medicine, Beijing 100048, China
Wang Zhongqi
Department of Orthopedic Surgery, The Fourth Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Musculoskeletal and Sports Medicine, Beijing 100048, China
Sun Xinyu
Department of Orthopedic Surgery, The Fourth Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Musculoskeletal and Sports Medicine, Beijing 100048, China
Wang Duanyang
Department of Orthopaedic Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing 100039, China
Chang Feifan
Department of Orthopedic Surgery, The Fourth Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Musculoskeletal and Sports Medicine, Beijing 100048, China
Zhang Haobo
Department of Orthopedic Surgery, The Fourth Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Musculoskeletal and Sports Medicine, Beijing 100048, China
Fu Pincong
Department of Orthopedic Surgery, The Fourth Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Musculoskeletal and Sports Medicine, Beijing 100048, China
Chen Ming
Department of Orthopedic Surgery, The Fourth Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Musculoskeletal and Sports Medicine, Beijing 100048, China
Li Yi
Department of Orthopedic Surgery, The Fourth Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Musculoskeletal and Sports Medicine, Beijing 100048, China
Yin Pengbin
Department of Orthopedic Surgery, The Fourth Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Musculoskeletal and Sports Medicine, Beijing 100048, China
Zhang Licheng
Department of Orthopedic Surgery, The Fourth Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Musculoskeletal and Sports Medicine, Beijing 100048, China
Tang Peifu
Department of Orthopedic Surgery, The Fourth Medical Center, Chinese PLA General Hospital, National Clinical Research Center for Musculoskeletal and Sports Medicine, Beijing 100048, China
·
DOI： 10.3760/cma.j.cn115530-20250103-00004
0
0
0
0
0
0
PDF下载
APP内阅读
摘要

目的探讨下肢制动后交感神经活性的改变及其参与调控骨骼肌废用性萎缩的作用。

方法实验分3部分：①选取8周龄C57雄性小鼠12只，随机分为空白对照组和后肢固定组（ n=6）：空白对照组小鼠不作干预，后肢固定组小鼠采用夹板固定双后肢2周，通过行为学、病理及分子水平等完成肌骨多维度表征。②选取8周龄C57雄性小鼠36只，随机分为空白对照组及后肢固定1、3、5、7、14 d组（ n=6）：空白对照组小鼠不作干预,正常饲养至14 d，后肢固定1、3、5、7、14 d组小鼠分别于夹板固定双后肢后1、3、5、7、14 d取材。检测血清中去甲肾上腺素(NE)水平及下丘脑室旁核（PVN）中交感神经活性标志物酪氨酸羟化酶（TH）的表达水平，观察交感神经活性是否发生可塑性改变。③选取8周龄C57雄性小鼠18只，随机分为空白对照组、后肢固定组、后肢固定给药组（ n=6）：空白对照组小鼠不作干预，后两组小鼠用夹板固定双后肢后分别给予连续2周的腹腔注射磷酸盐缓冲液和普萘洛尔盐酸盐溶液，比较3组小鼠的骨骼肌相关参数等。

结果①与空白对照组比较，后肢固定组小鼠的骨骼肌质量及功能显著下降，差异均有统计学意义（ P<0.05）。②后肢固定1、3、5、7、14 d组小鼠血清NE水平[（3.27±1.03）、（9.21±1.05）、（6.36±0.88）、（3.84±1.00）、（3.91±0.75）ng/mL]和PVN中TH +细胞占比（42.00%±5.38%、61.67%±5.57%、55.82%±3.11%、50.90%±2.53%、39.17%±9.07%）均显著高于空白对照组小鼠[（1.81±0.72）ng/mL、23.33%±5.50%]，差异均有统计学意义（ P<0.05）。③后肢固定给药组小鼠腓肠肌湿重[（93.50±4.32）mg]、胫骨前肌肌纤维横截面积[（1 180.00±95.09）μm 2]较后肢固定组小鼠增加[(80.83±9.99) mg、(907.80±121.00) μm 2]，差异均有统计学意义（ P<0.05）。

结论小鼠后肢固定后骨骼肌废用性萎缩模型中，发生交感神经系统过度激活，抑制交感神经活性可减轻下肢骨骼肌萎缩的程度。

下肢;肌，骨骼;肌萎缩;交感神经系统;去甲肾上腺素;下丘脑室旁核;制动
ABSTRACT

ObjectiveTo investigate the changes in sympathetic nerve activity after lower limb immobilization and the role of sympathetic nerve in regulating disuse atrophy of skeletal muscles.

MethodsThe experiment was divided into the following 3 parts: ① Twelve 8-week-old male C57 mice were randomly divided into a blank control group and a hind limb fixation group ( n=6). The blank control group received no intervention while the hind limb fixation group received splint fixation of the hind limbs for 2 weeks before the musculoskeletal multi-dimensional characterization was completed at the behavioral, pathological and molecular levels. ② Thirty-six 8-week-old male C57 mice were selected and randomly divided into a control group and 5 hind limb fixation groups (for 1, 3, 5, 7 and 14 days) ( n=6). The control group was fed normally until 14 days without any intervention while the 5 hind limb fixation groups were sampled after fixation for 1, 3, 5, 7 and 14 days, respectively. The level of norepinephrine in the serum and the expression level of tyrosine hydroxylase (TH), a marker of sympathetic nerve activity in the paraventricular nucleus of hypothalamus (PVN), were detected to observe the plasticity of sympathetic nerve activity. ③ Eighteen 8-week-old male C57 mice were selected and randomly divided into a blank control group, a hind limb fixation group and a hind limb fixation plus medication group ( n=6). The blank control group received no intervention while the 2 fixation groups were injected with phosphate buffer (PBS) and propranolol hydrochloride solution for 2 consecutive weeks, respectively. The parameters related to the skeletal muscles were compared between the 3 groups.

Results① Compared with the control group, the mass and function of skeletal muscles in the hind limb fixation group were statistically significantly decreased ( P<0.05). ② The levels of serum norepinephrine [(3.27±1.03) ng/mL, (9.21±1.05) ng/mL, (6.36±0.88) ng/mL, (3.84±1.00) ng/mL, and (3.91±0.75) ng/mL] and the PVN TH levels (42.00%±5.38%, 61.67%±5.57%, 55.82%±3.11%, 50.90%±2.53%, and 39.17%±9.07%) in the 5 hind limb fixation groups (for 1, 3, 5, 7 and 14 days) were significantly higher than those in the control group [(1.81±0.72)] ng/mL and 23.33%±5.50%] ( P<0.05). ③ The wet weight of the gastrocnemius muscle [(93.50±4.32) mg] and the cross-section area of the tibial anterior muscle [(1,180.00±95.09) μm 2] in the hind limb fixation plus medication group were increased significantly compared with those in the hind limb fixation group [(80.83±9.99) mg and (907.80±121.00) μm 2] ( P<0.05).

ConclusionsOveractivation of the sympathetic nervous system occurs in the mice model of skeletal muscle disuse atrophy after hind limb fixation. Inhibition of sympathetic nerve activity may reduce the severity of skeletal muscle atrophy at the lower limbs.

Lower extremity;Muscle, skeletal;Muscular atrophy;Sympathetic nerve;Norepinephrine;Paraventricular nucleus of hypothalamus;Immobilization
Tang Peifu, Email: mocdef.6ab21103gnatfp
Copyright by Chinese Medical Association
No content published by the journals of Chinese Medical Association may be reproduced or abridged without authorization. Please do not use or copy the layout and design of the journals without permission.
All articles published represent the opinions of the authors, and do not reflect the official policy of the Chinese Medical Association or the Editorial Board, unless this is clearly specified.
引用本文

程栋梁,张明铭,刘江,等. 交感神经参与调控骨骼肌废用性萎缩的初步探究[J]. 中华创伤骨科杂志,2025,27(03)：242-249.

DOI:10.3760/cma.j.cn115530-20250103-00004

PERMISSIONS

Request permissions for this article from CCC.

评价本文
*以上评分为匿名评价

版权归中华医学会所有。

未经授权，不得转载、摘编本刊文章，不得使用本刊的版式设计。

除非特别声明，本刊刊出的所有文章不代表中华医学会和本刊编委会的观点。

下肢骨折的发病率高、并发症多，严重影响患者的健康 [ 1 ]。下肢骨折后制动会使骨骼肌质量及功能迅速受损 [ 2 ]。有研究表明仅1周的卧床休息即可损失1.4 kg的肌肉质量 [ 3 , 4 ]，这种骨骼肌质量的损失可对骨折患者住院时间及康复疗效产生重要影响 [ 5 ]。同时，骨骼肌废用性萎缩也可引起代谢异常 [ 6 , 7 , 8 ]，如体脂量增加、胰岛素抵抗等。因此，防治下肢骨折制动后引起的骨骼肌废用性萎缩具有重要临床意义。尽管目前有针对骨骼肌废用性萎缩的干预策略，如抗阻运动、营养治疗及物理治疗等，但均存在诸多局限性 [ 9 ]。因此，亟待深入探讨骨骼肌废用性萎缩的疾病机制、开发新的治疗手段。
既往研究表明，骨骼肌作为机体代谢与运动的重要执行器官，具有显著的可塑性特征，这种动态平衡受到激素水平、营养状态及神经系统等的多维度调控 [ 10 , 11 , 12 ]，其中肾上腺素能受体介导的交感神经调控在骨骼肌稳态中具有重要意义 [ 13 , 14 ]。交感神经系统在骨骼肌稳态中呈现双向调控特征：交感神经可促进干细胞的干性，有利于骨骼肌损伤的修复 [ 15 ]；反之肾上腺素能受体过度激活可加重肌管萎缩 [ 16 ]，这种矛盾现象提示交感神经系统在骨骼肌稳态维持中可能具有微环境依赖性的调控特征，在制动导致的骨骼肌废用性萎缩中，交感神经如何参与调控骨骼肌萎缩尚未明确。
本研究通过构建下肢制动导致的废用性骨骼肌萎缩模型 [ 17 ]，探讨制动微环境诱导的交感神经可塑性特征，以及交感神经系统参与调控骨骼肌萎缩的具体作用，以期为下肢制动导致的骨骼肌废用性萎缩的治疗提供新思路、开发新靶点。
试读结束，您可以通过登录机构账户或个人账户后获取全文阅读权限。
参考文献
[1]
Aloraibi S , Booth V , Robinson K ,et al. Optimal management of older people with frailty non-weight bearing after lower limb fracture: a scoping review[J]. Age Ageing, 2021,50(4):1129-1136. DOI: 10.1093/ageing/afab071 .
返回引文位置Google Scholar
百度学术
万方数据
[2]
肖向宇,万泽东,张彦歌,等. 老年髋部骨折患者术后30 d发生主要并发症的风险预测模型构建及验证研究[J]. 中华创伤骨科杂志, 2024,26(9):775-782. DOI: 10.3760/cma.j.cn115530-20240201-00051 .
返回引文位置Google Scholar
百度学术
万方数据
Xiao XY , Wan ZD , Zhang YG ,et al. Construction and validation of a risk prediction model for major complications 30 days after surgery in elderly patients with hip fracture[J]. Chin J Orthop Trauma, 2024,26(9):775-782. DOI: 10.3760/cma.j.cn115530-20240201-00051 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[3]
Gibson JN , Halliday D , Morrison WL ,et al. Decrease in human quadriceps muscle protein turnover consequent upon leg immobilization[J]. Clin Sci (Lond), 1987,72(4):503-509. DOI: 10.1042/cs0720503 .
返回引文位置Google Scholar
百度学术
万方数据
[4]
Dirks ML , Wall BT , van de Valk B ,et al. One week of bed rest leads to substantial muscle atrophy and induces whole-body insulin resistance in the absence of skeletal muscle lipid accumulation[J]. Diabetes, 2016,65(10):2862-2875. DOI: 10.2337/db15-1661 .
返回引文位置Google Scholar
百度学术
万方数据
[5]
Suetta C , Hvid LG , Justesen L ,et al. Effects of aging on human skeletal muscle after immobilization and retraining[J]. J Appl Physiol (1985), 2009,107(4):1172-1180. DOI: 10.1152/japplphysiol.00290.2009 .
返回引文位置Google Scholar
百度学术
万方数据
[6]
Biensϕ RS , Ringholm S , Kiilerich K ,et al. GLUT4 and glycogen synthase are key players in bed rest-induced insulin resistance[J]. Diabetes, 2012,61(5):1090-1099. DOI: 10.2337/db11-0884 .
返回引文位置Google Scholar
百度学术
万方数据
[7]
Alibegovic AC , Hϕjbjerre L , Sonne MP ,et al. Impact of 9 days of bed rest on hepatic and peripheral insulin action, insulin secretion, and whole-body lipolysis in healthy young male offspring of patients with type 2 diabetes[J]. Diabetes, 2009,58(12):2749-2756. DOI: 10.2337/db09-0369 .
返回引文位置Google Scholar
百度学术
万方数据
[8]
Stuart CA , Shangraw RE , Prince MJ ,et al. Bed-rest-induced insulin resistance occurs primarily in muscle[J]. Metabolism, 1988,37(8):802-806. DOI: 10.1016/0026-0495(88)90018-2 .
返回引文位置Google Scholar
百度学术
万方数据
[9]
Nunes EA , Stokes T , McKendry J ,et al. Disuse-induced skeletal muscle atrophy in disease and nondisease states in humans: mechanisms, prevention, and recovery strategies[J]. Am J Physiol Cell Physiol, 2022,322(6):C1068-C1084. DOI: 10.1152/ajpcell.00425.2021 .
返回引文位置Google Scholar
百度学术
万方数据
[10]
Egerman MA , Glass DJ . Signaling pathways controlling skeletal muscle mass[J]. Crit Rev Biochem Mol Biol, 2014,49(1):59-68. DOI: 10.3109/10409238.2013.857291 .
返回引文位置Google Scholar
百度学术
万方数据
[11]
Palus S , von Haehling S , Springer J . Muscle wasting: an overview of recent developments in basic research[J]. J Cachexia Sarcopenia Muscle, 2014,5(3):193-198. DOI: 10.1007/s13539-014-0157-7 .
返回引文位置Google Scholar
百度学术
万方数据
[12]
Deane CS , Piasecki M , Atherton PJ . Skeletal muscle immobilisation-induced atrophy: mechanistic insights from human studies[J]. Clin Sci (Lond), 2024,138(12):741-756. DOI: 10.1042/CS20231198 .
返回引文位置Google Scholar
百度学术
万方数据
[13]
Delbono O , Rodrigues ACZ , Bonilla HJ ,et al. The emerging role of the sympathetic nervous system in skeletal muscle motor innervation and sarcopenia[J]. Ageing Res Rev, 2021,67:101305. DOI: 10.1016/j.arr.2021.101305 .
返回引文位置Google Scholar
百度学术
万方数据
[14]
Rodrigues ACZ , Wang ZM , Messi ML ,et al. Heart and neural crest derivative 2-induced preservation of sympathetic neurons attenuates sarcopenia with aging[J]. J Cachexia Sarcopenia Muscle, 2021,12(1):91-108. DOI: 10.1002/jcsm.12644 .
返回引文位置Google Scholar
百度学术
万方数据
[15]
Yuan S , Zheng S , Zheng K ,et al. Sympathetic activity is correlated with satellite cell aging and myogenesis via β 2-adrenoceptor [J]. Stem Cell Res Ther, 2021,12(1):505. DOI: 10.1186/s13287-021-02571-8 .
返回引文位置Google Scholar
百度学术
万方数据
[16]
Matsukawa S , Kai S , Seo H ,et al. Activation of the β -adrenergic receptor exacerbates lipopolysaccharide-induced wasting of skeletal muscle cells by increasing interleukin-6 production [J]. PLoS One, 2021,16(5):e0251921. DOI: 10.1371/journal.pone.0251921 .
返回引文位置Google Scholar
百度学术
万方数据
[17]
Baek KW , Jung YK , Kim JS ,et al. Rodent model of muscular atrophy for sarcopenia study[J]. J Bone Metab, 2020,27(2):97-110. DOI: 10.11005/jbm.2020.27.2.97 .
返回引文位置Google Scholar
百度学术
万方数据
[18]
Di Bona A , Vita V , Costantini I ,et al. Towards a clearer view of sympathetic innervation of cardiac and skeletal muscles[J]. Prog Biophys Mol Biol, 2020,154:80-93. DOI: 10.1016/j.pbiomolbio.2019.07.003 .
返回引文位置Google Scholar
百度学术
万方数据
[19]
谢昀,邹文选,方芳,等. 腓肠神经的交感成分及其对腓肠神经营养血管皮瓣血流动力学影响的探查[J]. 中国临床解剖学杂志, 2017,35(1):25-30. DOI: 10.13418/j.issn.1001-165x.2017.01.006 .
返回引文位置Google Scholar
百度学术
万方数据
Xie Y , Zou WX , Fang F ,et al. The impact on hemodynamics of proximally-based sural neurovascular flap by different management of sural nerve[J]. Chinese Journal of Clinical Anatomy, 2017,35(1):25-30. DOI: 10.13418/j.issn.1001-165x.2017.01.006 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[20]
Hotta H , Iimura K , Watanabe N ,et al. Sympathetic modulation of hindlimb muscle contractility is altered in aged rats[J]. Sci Rep, 2023,13(1):7504. DOI: 10.1038/s41598-023-33821-9 .
返回引文位置Google Scholar
百度学术
万方数据
[21]
Dombrecht D , Van Daele U , Van Asbroeck B ,et al. Molecular mechanisms of post-burn muscle wasting and the therapeutic potential of physical exercise[J]. J Cachexia Sarcopenia Muscle, 2023,14(2):758-770. DOI: 10.1002/jcsm.13188 .
返回引文位置Google Scholar
百度学术
万方数据
[22]
Rehou S , de Brito Monteiro L , Auger C ,et al. Propranolol normalizes metabolomic signatures thereby improving outcomes after burn[J]. Ann Surg, 2023,278(4):519-529. DOI: 10.1097/SLA.0000000000005973 .
返回引文位置Google Scholar
百度学术
万方数据
[23]
陈绍娟,向力,江淼,等. 异丙肾上腺素在C2C12细胞分化中的作用及机制[J]. 中国细胞生物学学报, 2017,39(9):1178-1187. DOI: 10.11844/cjcb.2017.09.0100 .
返回引文位置Google Scholar
百度学术
万方数据
Chen SJ , Xiang L , Jiang M ,et al. Isoprenaline induced muscle atrophy by inhibiting the differentiation of C2C12 cells into skeletal muscle cells[J]. Chinese Journal of Cell Biology, 2017,39(9):1178-1187. DOI: 10.11844/cjcb.2017.09.0100 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[24]
Kim YS , Sainz RD . Beta-adrenergic agonists and hypertrophy of skeletal muscles[J]. Life Sci, 1992,50(6):397-407. DOI: 10.1016/0024-3205(92)90374-x .
返回引文位置Google Scholar
百度学术
万方数据
[25]
Ryall JG , Schertzer JD , Lynch GS . Attenuation of age-related muscle wasting and weakness in rats after formoterol treatment: therapeutic implications for sarcopenia[J]. J Gerontol A Biol Sci Med Sci, 2007,62(8):813-823. DOI: 10.1093/gerona/62.8.813 .
返回引文位置Google Scholar
百度学术
万方数据
[26]
Guo Q , Chen N , Patel K ,et al. Unloading-induced skeletal interoception alters hypothalamic signaling to promote bone loss and fat metabolism[J]. Adv Sci (Weinh), 2023,10(35):e2305042. DOI: 10.1002/advs.202305042 .
返回引文位置Google Scholar
百度学术
万方数据
[27]
Gao F , Hu Q , Chen W ,et al. Brain regulates weight bearing bone through PGE2 skeletal interoception: implication of ankle osteoarthritis and pain[J]. Bone Res, 2024,12(1):16. DOI: 10.1038/s41413-024-00316-w .
返回引文位置Google Scholar
百度学术
万方数据
[28]
Ohmichi Y , Ohmichi M , Tashima R ,et al. Physical disuse contributes to widespread chronic mechanical hyperalgesia, tactile allodynia, and cold allodynia through neurogenic inflammation and spino-parabrachio-amygdaloid pathway activation[J]. Pain, 2020,161(8):1808-1823. DOI: 10.1097/j.pain.0000000000001867 .
返回引文位置Google Scholar
百度学术
万方数据
备注信息
A
唐佩福, Email: mocdef.6ab21103gnatfp
B

程栋梁：实验操作、统计学分析、论文撰写；张明铭：实验指导、论文修改；刘江、沈俊民、王中奇、孙新宇、王端阳、常非凡、张皓博、付品聪：实验操作、数据整理；陈铭、李毅：研究指导；尹鹏滨、张里程、唐佩福：经费支持、研究指导、方案审定

C
所有作者声明无利益冲突
D
国家自然科学基金 (82472447，82204944)
评论 （0条）
注册
登录
时间排序
暂无评论，发表第一条评论抢沙发
最新推荐
更多
难复性股骨转子间骨折的2021分型与复位技巧研究
佟大可 等
中华创伤骨科杂志 2022,24(03)
股骨转子间骨折复位质量判断标准的研究进展
李世杰 等
中华创伤骨科杂志 2022,24(09)
股骨转子间骨折初次手术失败的翻修策略和研究进展
张伟 等
中华创伤骨科杂志 2021,23(03)
股骨转子间骨折术后内固定失效的危险因素研究进展
聂少波 等
中华创伤骨科杂志 2021,23(03)
MedAI助手（体验版）
文档即答
智问智答
机器翻译
回答内容由人工智能生成，我社无法保证其准确性和完整性，该生成内容不代表我们的态度或观点，仅供参考。
生成快照
文献快照

你好，我可以帮助您更好的了解本文，请向我提问您关注的问题。

0/2000

《中华医学会杂志社用户协议》 | 《隐私政策》

《SparkDesk 用户协议》 | 《SparkDesk 隐私政策》

网信算备340104764864601230055号 | 网信算备340104726288401230013号

技术支持：

历史对话
本文全部
还没有聊天记录
设置
模式
纯净模式沉浸模式
字号
小中大