延迟性肌肉酸痛与骨骼肌卫星细胞:骨骼肌损伤的修复

背景:长时间或高强度运动出现的骨骼肌纤维损伤是导致骨骼肌损伤直接原因。目的:文章从修复骨骼肌损伤的客观实际出发,提出骨骼肌损伤后产生的延迟性肌肉酸痛与骨骼肌卫星细胞之间存在某种关系。方法:检索1961年2月至2015年2月中国知网和Pub Med数据库中相关文献资料,中文检索词:延迟性肌肉酸痛;骨骼肌损伤;骨骼肌卫星细胞;调节因子;英文检索词:Delayed Onset Muscle Soreness;Satellite Cells,Skeletal Muscle;Myogenic Regulatory Factors。纳入59篇国内外文献,对骨骼肌损伤伴随的延迟性肌肉疼痛的发生机制做一探讨。结果与结论:骨骼肌微损伤主要涉及肌细胞生物膜、细胞骨架、肌小节、线粒体等超微结构的破坏和细胞代谢功能紊乱,进而导致骨骼肌收缩功能下降,期间常伴有延迟性肌肉酸痛,其中以离心运动对骨骼肌纤维的微细损伤最为显著;延迟性酸痛的骨骼肌特殊微环境一定程度上刺激骨骼肌卫星细胞生长因子的分泌,持续大强度离心运动引发的延迟性肌肉酸痛的发生时序与骨骼肌卫星细胞增殖时序存在一定的相关性。     

运动与不同组织细胞凋亡*

背景：细胞凋亡程序可被运动刺激诱发启动造成细胞死亡。 目的：分析运动训练对不同组织细胞凋亡的影响,探讨运动训练引起的不同组织细胞凋亡与运动性疲劳,运动损伤,运动心脏重塑,运动性心肌微损伤,运动性免疫抑制的关系。 方法：应用计算机检索Medline数据库1990-01/2010-05期间运动训练与细胞凋亡关系的文章,检索词为“apoptosis”。同时检索Ginii数据库2000-01/2010-06期间运动训练与细胞凋亡关系的文章,检索词为“アポトーシス,運動”。同时计算机检索中国期刊全文数据库2000-01/2010-05期间运动训练与细胞凋亡相关的文章,检索词为“细胞凋亡,运动训练,骨骼肌,心肌,淋巴细胞,肝肾细胞”。 结果与结论：无论是单次运动还是系统运动训练,都可以对骨骼肌、心肌、肝肾及淋巴细胞的凋亡产生影响,并呈现细胞凋亡水平随运动强度的提高而提高,因此细胞凋亡与运动性骨骼肌微损伤,运动心脏重塑,运动性心肌微损伤,运动性免疫抑制的关系密切。 关键词：细胞凋亡;运动训练;骨骼肌细胞;心肌细胞;淋巴细胞 doi:10.3969/j.issn.1673-8225.2012.11.036     

骨骼肌的运动适应机制

背景：骨骼肌运动适应机制的研究对提高运动成绩,预防和治疗一些代谢紊乱性疾病具有重要意义。 目的：探讨骨骼肌运动适应的机制。 方法：应用计算机检索PubMed数据库和中文期刊全文数据库2011-03前发表的相关文章,检索词分别为“skeletal muscle, exercise, adaptation, cytoskeleton, dystrophin”和“骨骼肌,运动,适应,骨架蛋白,肌营养不良蛋白”,共检索到56篇文献,纳入所述内容与骨骼肌运动适应机制相关的文献,排除重复性研究,保留31篇进行综述。 结果与结论：激烈的运动使肌肉结构和细胞代谢产生应激反应,包括肌肉损伤和氧化应激反应。高强度的离心运动可造成肌肉超微结构损伤,但运动性肌损伤后存在肌肉再重建反应。运动训练可促进健康的个体对一氧化氮系统产生各种各样的适应,通过各种机制增强骨骼肌的生物学有效性,这些适应性变化可有效增加运动能力,对心血管系统具有保护作用。目前,大多数人类骨骼肌运动适应机制还没有被发现。     

小胶质细胞与帕金森病

背景：由于多巴胺能神经元对氧化应激特别敏感,小胶质细胞的重要特点之一是易活化,而活化的小胶质细胞是氧自由基产生的主要来源,因此小胶质细胞的激活在帕金森病的发病和病情进展中具有更加重要的作用。 目的：总结讨论小胶质细胞与帕金森病的相互关系。 方法：由第一作者用计算机检索中国期刊全文数据库(CNKI：2000/2010)和Medline数据库(2000/2010),检索词分别为“帕金森病,小胶质细胞”和“Parkinson’s disease, Microglia”,从小胶质细胞激活后产生的细胞因子、毒性物质对帕金森病发病的影响与抑制小胶质细胞的激活,阻止神经毒性因子的损害作用进而阻止帕金森病的进展2方面进行总结,对小胶质细胞与帕金森病的相互关系作相关介绍。 结果与结论：共检索到112篇文章,按纳入和排除标准对文献进行筛选,共纳入27篇文章。结果表明小胶质细胞的激活会损伤多巴胺能神经元,从而引发帕金森病。而帕金森病的发生发展则使多巴胺递质进一步减少、继续损伤多巴胺能神经元并释放炎性因子促使小胶质细胞激活。抑制小胶质细胞的激活则有可能阻止帕金森病的进展。     

骨骼肌中卫星细胞衰老生物学机制及潜在的应对策略

背景：卫星细胞是一种肌源性干细胞，位于肌纤维膜与基底膜之间，但尚未有综述完全揭示卫星细胞衰老机制及其潜在应对策略，这对于当前减缓骨骼肌老化的策略应用难以起到有效的指导效果。目的：综述骨骼肌中卫星细胞衰老的机制及其相关减缓其衰老的应对策略。方法：检索各数据库时间截至2023年5月，包括Web of Science、PubMed、中国知网、万方和维普数据库。英文检索词：“Skeletal muscle,satellite cells,aging,mechanism,solution strategye”；中文检索词：“骨骼肌，卫星细胞，衰老，老化，机制，应对策略”。经过严格按照纳入和排除标准进行筛选，最终纳入78篇文献进行综述分析。结果与结论：(1)卫星细胞位于肌纤维膜与基底膜之间，具有增殖和分化潜能，通常处于静息状态，但在肌肉组织受刺激时会被激活并参与修复和恢复正常组织结构的过程，衰老会导致卫星细胞数量减少，并引发肌力和耐力的下降等症状。(2)卫星细胞衰老的机制主要涉及再生能力下降、串扰能力随生态位变化、年龄依赖性损失和异质性变化，衰老的卫星细胞数量减少以及活性降低会导致肌肉再生速度变慢...     

骨骼肌细胞与热休克蛋白

背景：骨骼肌含有多种热休克蛋白,可能具有重要的生理功能。 目的：综述骨骼肌热休克蛋白的特性,以及骨骼肌热休克蛋白在生理及病理情况下表达的意义。 方法：以“热休克蛋白,骨骼肌,运动,缺血再灌注”为中文检索词,以“heat shock proteins, skeletal muscle, exercise, ischemia-reperfusion”为英文检索词,应用计算机检索Pubmed数据库和中文期刊全文数据库2010-06前发表的相关文章。纳入与骨骼肌细胞热休克蛋白研究相关的文献,排除重复性研究。 结果与结论：共检索到197篇文献,排除无关重复的文献,保留35篇文献进行综述。目前研究证实骨骼肌含有多种热休克蛋白,主要有小热休克蛋白,热休克蛋白70,热休克蛋白60和热休克蛋白90等。热休克蛋白作为应激的指标,可以反映运动时细胞内发生的变化,对监控过度训练有重要意义。同时热休克蛋白在过度训练或肌肉损伤时对保持肌肉功能起重要作用。     

去神经支配骨骼肌萎缩的多种治疗

背景：骨骼肌去神经支配后出现肌萎缩和收缩功能的丧失,肌纤维发生与萎缩相关的一系列的形态学和组织学的变化。近年来随着技术水平及理论研究的进展,治疗效果有了较大的提高,但仍未达到满意的效果。 目的：总结并讨论近年来有关去神经支配骨骼肌萎缩的治疗新进展,为肌肉功能的恢复提供理论基础。 方法：由第一作者用计算机检索中国期刊全文数据库(CNKI：2000/2010)和Medline数据库(2000/2010),检索词分别为“去神经支配,骨骼肌,肌萎缩,治疗”和“denervated,skeletal muscles,atrophy,treatment”。共检索到135篇文章,按纳入和排除标准对文献进行筛选,共纳入30篇文章,从物理治疗、神经修复和植入、细胞移植、药物、基因和中药治疗等方面进行总结和分析。 结果与结论：近年来去神经支配骨骼肌的治疗取得了很大进展,但这些方法只能在一定程度上缓解骨骼肌萎缩,在一段时间内维持肌肉的生理功能。目前研究随着去神经支配骨骼肌萎缩机制的阐明,针对性的治疗措施将会取得更好的效果。     

骨骼肌再生过程中卫星细胞调控机制及其生态位信号的作用

背景：卫星细胞是骨骼肌包含的一种特定的成体干细胞群，可促进损伤骨骼肌的再生重建，但其具体机制尚不完善。目的：综述骨骼肌再生过程中卫星细胞调控作用以及卫星细胞与其生态位信号相互作用的机制，旨在总结现有知识的基础上提供新的研究思路和角度。方法：检索Web of Science、PubMed、中国知网(CNKI)、万方、维普等数据库2002年1月至2022年6月发表的文献。英文检索词：muscle,skeletal muscle,muscle injury,stem cells,satellite cells,muscle repair等；中文检索词：骨骼肌，骨骼肌再生，骨骼肌重建，卫星细胞，生态位等。共纳入66篇文献进行整理和分析。结果与结论：(1)卫星细胞存在于骨骼肌中，其既有助于损伤后新肌纤维的形成，亦有助于已存在的成年肌纤维有效生长。(2)卫星细胞中的静止卫星细胞被激活后，骨骼肌再生过程中卫星细胞的增殖、分化和融合形成肌纤维等步骤均会受到其内在不同机制调控作用的影响。(3)卫星细胞可与所处生态位信号中的肌纤维、细胞外基质、骨骼肌交界位、纤维生成祖细胞、免疫细胞以及内皮细胞相互作用促进...     

肌肉组织工程研究现状及对运动性肌肉损伤的作用

背景：高水平快节奏的体育运动比赛中容易造成肌肉运动损伤,肌肉组织工程为其修复带来希望。 目的：综述肌肉组织工程研究的现状,为运动性肌肉损伤组织工程学研究提供理论基础。 方法：以“tissue engineering, anterior cruciate ligament repair, biological material scaffold, cytokines, seed cells”为关键词,采用计算机检索Pubmed数据库中1994-01/2010-12的相关文章。纳入与运动性肌肉损伤及肌肉组织工程相关的文章;排除重复研究或Meta分析类文章。 结果与结论：共纳入15篇文献,目前的研究重点包括肌肉组织工程重建、细胞外基质复合材料、肌肉组织工程种子细胞的来源、基质支架4个方面。目前的研究表明肌肉组织工程对运动性肌肉损伤的治疗有良好的应用前景。但在实际应用中,肌肉组织工程的种子细胞的选择、支架材料的构建、细胞外基质复合材料研究和组织的相容性等仍是肌肉组织工程学方面的难点问题。     

骨骼肌重塑中的钙调神经磷酸酶信号转导通路

背景：骨骼肌重塑是骨骼肌对多种刺激因素所产生的形态结构与代谢机能的适应性变化。近几年关于钙调神经磷酸酶(CaN )/ (NFATS)在骨骼肌重塑中的作用备受关注。 目的：探讨钙调神经磷酸酶在骨骼肌从无氧转向有氧的代谢重塑、肌纤维类型转化以及在骨骼肌肥大过程中的信号转导作用。 方法：由第一作者用计算机检索ISI Web of knowledge数据库(1998/2010),检索词为 “calcineurin,skeletal muscle,hypertrophy,NFAT,myofiber type”,语言设定为英文。从钙调神经磷酸酶信号系统在骨骼肌代谢、肌纤维类型转换和肌肉肥大中的作用方面进行总结,对其调节机制、肌肉重塑等方面进行介绍。 结果与结论：共检索到186篇文章,按纳入和排除标准对文献进行筛选,共纳入33篇文章。结果表明CaN/NFATS信号激活有助于Ⅰ型肌纤维分化,提高线粒体有氧代谢能力,但骨骼肌对耐力运动的适应并不绝对依赖CaN。CaN/NFATS转导通路有可能通过转录激活utrophin A来调控骨骼肌的肥大反应。由此可知钙调神经磷酸酶参与骨骼肌代谢、纤维转化和肥大的重塑过程,调节骨骼肌对刺激产生适应性应答反应。     

Cellular and molecular regulation of muscle regeneration

Under normal circumstances, mammalian adult skeletal muscle is a stable tissue with very little turnover of nuclei. However, upon injury, skeletal muscle has the remarkable ability to initiate a rapid and extensive repair process preventing the loss of muscle mass. Skeletal muscle repair is a highly synchronized process involving the activation of various cellular responses. The initial phase of muscle repair is characterized by necrosis of the damaged tissue and activation of an inflammatory response. This phase is rapidly followed by activation of myogenic cells to proliferate, differentiate, and fuse leading to new myofiber formation and reconstitution of a functional contractile apparatus. Activation of adult muscle satellite cells is a key element in this process. Muscle satellite cell activation resembles embryonic myogenesis in several ways including the de novo induction of the myogenic regulatory factors. Signaling factors released during the regenerating process have been identified, but their functions remain to be fully defined. In addition, recent evidence supports the possible contribution of adult stem cells in the muscle regeneration process. In particular, bone marrow-derived and muscle-derived stem cells contribute to new myofiber formation and to the satellite cell pool after injury.     

miRNAs在骨骼肌损伤修复过程中的调控作用

不合理的运动方式经常会引起骨骼肌损伤,骨骼肌损伤后,成体生肌性干细胞(主要是卫星细胞)被激活,进而增殖分化,与原来肌纤维融合完成修复过程。miRNAs是一种在后转录水平调节基因表达的非编码RNAs,在骨骼肌损伤与修复过程中主要通过靶向抑制一些转录因子、转录激活途径关键酶、细胞通讯连接重要蛋白以及各种信号通路中关键蛋白的翻译而发挥调控作用。为了更好地了解miRNAs在骨骼肌损伤修复过程中的作用,本文通过对miRNAs在骨骼肌损伤与修复过程中卫星细胞不同生物学状态以及信号通路等方面的作用和研究现状做一综述。     

The role of neutrophils in injury and repair following muscle stretch

Stretch injury to the myotendinous junction is a common problem in competitive athletes and those involved in regular physical activity. The major risk factor for recurrent injury appears to be the primary injury itself. Physicians, physical therapists, athletic trainers and athletes alike continue to search for optimal treatment and prevention strategies. Acute inflammation is regarded as the body's generalized protective response to tissue injury. An especially important and unexplored aspect of inflammation following injury is the role of inflammatory cells in extending injury and possibly directing muscle repair. It has been suggested that the inflammatory reaction, although it typically represents a reaction to damage and necrosis, may even bring about some local damage of its own and therefore increase the possibility for scarring and fibrosis. Limiting certain aspects of inflammation may theoretically reduce muscle damage as well as signals for muscle scarring. Here we focus on the role of neutrophils in injury and repair of stretch-injured skeletal muscle. A minimally invasive model that generates a reproducible injury to rabbit skeletal muscle is presented. We present a plausible theory that neutrophil-derived oxidants resulting from the initial stretch injury are responsible for extending the damage. An anti-CD11b antibody that blocks the neutrophil's respiratory burst is employed to reduce myofibre damage. An intriguing area that is currently being explored in our laboratory and others is the potential role for neutrophils to contribute to muscle growth and repair. It may be possible that neutrophils facilitate muscle repair through removal of tissue debris as well as by activation of satellite cells. Recent and ongoing investigations point to interleukin-6 as a possible key cytokine in muscle inflammation and repair. Studies to elucidate a clearer understanding of this possibility will be reviewed.     

Regenerative function of immune system: Modulation of muscle stem cells

Ageing is characterised by progressive deterioration of physiological systems and the loss of skeletal muscle mass is one of the most recognisable, leading to muscle weakness and mobility impairments. This review highlights interactions between the immune system and skeletal muscle stem cells (widely termed satellite cells or myoblasts) to influence satellite cell behaviour during muscle regeneration after injury, and outlines deficits associated with ageing. Resident neutrophils and macrophages in skeletal muscle become activated when muscle fibres are damaged via stimuli (e.g. contusions, strains, avulsions, hyperextensions, ruptures) and release high concentrations of cytokines, chemokines and growth factors into the microenvironment. These localised responses serve to attract additional immune cells which can reach in excess of 1 × 10⁵ immune cell/mm³ of skeletal muscle in order to orchestrate the repair process. T-cells have a delayed response, reaching peak activation roughly 4 days after the initial damage. The cytokines and growth factors released by activated T-cells play a key role in muscle satellite cell proliferation and migration, although the precise mechanisms of these interactions remain unclear. T-cells in older people display limited ability to activate satellite cell proliferation and migration which is likely to contribute to insufficient muscle repair and, consequently, muscle wasting and weakness. If the factors released by T-cells to activate satellite cells can be identified, it may be possible to develop therapeutic agents to enhance muscle regeneration and reduce the impact of muscle wasting during ageing and disease.     

Muscle satellite (stem) cell activation during local tissue injury and repair

In post-mitotic tissues, damaged cells are not replaced by new cells and hence effective local tissue repair mechanisms are required. In skeletal muscle, which is a syncytium, additional nuclei are obtained from muscle satellite (stem) cells that multiply and then fuse with the damaged fibres. Although insulin-like growth factor-I (IGF-l) had been previously implicated, it is now clear that muscle expresses at least two splice variants of the IGF-I gene: a mechanosensitive, autocrine, growth factor (MGF) and one that is similar to the liver type (IGF-IEa). To investigate this activation mechanism, local damage was induced by stretch combined with electrical stimulation or injection of bupivacaine in the rat anterior tibialis muscle and the time course of regeneration followed morphologically. Satellite cell activation was studied by the distribution and levels of expression of M-cadherin (M-cad) and related to the expression of the two forms of IGF-I. It was found that the following local damage MGF expression preceded that of M-cad whereas IGF-IEa peaked later than M-cad. The evidence suggests therefore that an initial pulse of MGF expression following damage is what activates the satellite cells and that this is followed by the later expression of IGF-IEa to maintain protein synthesis to complete the repair.     

细胞生长因子修复骨骼肌损伤

BACKGROUND: A variety of cell growth factors are involved in skeletal muscle regeneration; moreover, these factors cooperate with each other to promote muscle repair and regeneration. OBJECTIVE: To explore the synergy mechanism of a variety of cell growth factors in promoting damage repair. METHODS: By using literature survey, Wanfang, CNKI and PubMed databases were searched for articles related to exercise-induced muscle damage and repair using the keywords of “cell growth factor; skeletal muscle damage;   repair; fibroblast growth factor” in Chinese and English, respectively. Research achievements related to exercise-induced muscle damage, molecular biological characteristics of cell growth factors and skeletal muscle injury repair are discussed. RESULTS AND CONCLUSION: Basic fibroblast growth factor plays a basic biological role to promote cell proliferation and angiogenesis, which is the strongest cytokine known to promote cell growth and reflects a very important role in skeletal muscle repair. Epidermal growth factor is synthesized by monocytes and ectodermal cells, which is prominent to stimulate the division and proliferation of a variety of tissues and cells, enhance cell movement, division and synthesis of interstitial protein. Insulin-like growth factors are a family of insulin-like growth factor 1-related and insulin-like growth factor 2-related peptides, which can promote muscle protein synthesis, promote muscle cell proliferation and differentiation, and participate in skeletal muscle regeneration and repair, thereby accelerating wound healing of the muscles. Neurotrophic factor is a kind of trace soluble substances around sensory neurons and produced by neuron-targeted cells, which can specifically promote neuronal growth and maintenance, and promote skeletal muscle repair. But studies on the synergy mechanism of a variety of cell growth factors in the repair of exercise-induced muscle damage are just at the initial stage, and further research is necessary.       

SD大鼠骨骼肌钝挫伤早期的组织病理变化

背景：骨骼肌钝挫伤后继续运动对骨骼肌组织愈合的影响目前还没有确切的定论。 目的：观察急性骨骼肌钝挫伤SD大鼠跑台运动后的组织病理变化。 方法：将64只SD大鼠随机分为正常对照组、模型组、自然愈合组、运动干预组,后3组建立左后肢腓肠肌中段骨骼肌钝挫伤模型,模型组造模后6 h处死取材,运动干预组进行跑台运动干预,自然愈合组继续饲养,但不进行运动干预。 结果与结论：自然愈合组、运动干预组大鼠急性腓肠肌钝挫伤后24 h~3 d内损伤肌肉组织中均出现大量炎细胞浸润,5 d时显著下降,同期内各时间点运动干预组炎细胞数显著多于自然愈合组(P < 0.05);7 d时两组炎细胞基本消失,伤后5 d两组均开始出现少量瘢痕组织,随时间延长而逐渐增加,7~14 d时运动干预组瘢痕组织面积显著高于自然愈合组(P < 0.01);伤后14 d两组瘢痕组织均仍有增多趋势。表明急性骨骼肌钝挫伤后早期运动训练可加重损伤局部炎性反应,并导致瘢痕组织过度形成,对损伤骨骼肌的修复存在负面影响。     

Satellite cell pool enhancement in rat plantaris muscle by endurance training depends on intensity rather than duration

Aim: Increases in the number of satellite cells are necessary for the maintenance of normal muscle function. Endurance training enhances the satellite cell pool. However, it remains unclear whether exercise intensity or exercise duration is more important to enhance the satellite cell pool. This study examined the effects of different intensity and duration of endurance training on the satellite cell pool in rat skeletal muscle. Methods: Forty‐one 17‐week‐old female Sprague–Dawley rats were assigned to control (n = 8), high intensity and high duration (n = 7), high intensity and low duration (n = 8), low intensity and high duration (n = 9) and low intensity and low duration (n = 9) groups. Training groups exercised 5 days per week on a motor driven treadmill for 10 weeks. After the training period, animals were anaesthetized and the plantaris muscles were removed, weighed and analysed for immunohistochemical and histochemical properties. Results: Although no significant differences were found in muscle mass, mean fibre area and myonuclei per muscle fibre between all groups, the percentage of satellite cells was significantly higher in the high‐intensity groups than in the other groups (P < 0.05). Conclusion: Increases in the satellite cell pool of skeletal muscle following endurance training depend on the intensity rather than duration of exercise.     

Flk-1+ adipose-derived mesenchymal stem cells differentiate into skeletal muscle satellite cells and ameliorate muscular dystrophy in mdx mice

Duchenne muscular dystrophy (DMD) is a severe hereditary disease characterized by the absence of dystrophin on the sarcolemma of muscle fiber. This absence results in widespread muscle damage and satellite cell activation. After depletion of the satellite cell pool, skeletal muscle is then invariably replaced by connective tissue, leading to progressive muscle weakness. Herein, we isolated Flk-1(+) mesenchymal stem cells (MSCs) from adult adipose tissue and induced them to differentiate into skeletal muscle cells in culture. Within mdx mice, an animal model of DMD, adipose tissue-derived Flk-1(+) MSCs (AD-MSCs) homed to and differentiated into cells that repaired injured muscle tissue. This repair correlated with reconstitution of dystrophin expression on the damaged fibers. Flk-1(+) AD-MSCs also differentiated into muscle satellite cells. This differentiation may have accounted for long-term reconstitution. These cells also differentiated into endothelial cells, thereby possibly improving fiber regeneration as a result of the induced angiogenesis. Therefore, Flk-1(+) AD-MSC transplants may repair muscular dystrophy.