背景:临床上治疗肌腱病的多种策略的短期效果较好而长期效果不佳,研究证明线粒体与肌腱病的发生发展有密切关系,但目前尚未总结出线粒体与肌腱病之间的关系和靶向线粒体治疗肌腱病的策略,不利于专科从业者及相关领域学者了解研究近况.目的:综述现有的临床或临床前原始研究,以期对线粒体功能障碍与肌腱病之间的关系、靶向线粒体治疗肌腱病的方法进行总结,并对未来线粒体在肌腱病中的评估和管理进行一定的展望.方法:检索PubMed、Web of Science、中国知网、万方和维普数据库中的相关文献.检索时限为2009年1月至2024年3月,英文检索词为"Tendinopathy,Tendons Injuries,Tendon,Tendons,Mitochondria,Mitochondria Dysfunction,Mitochondria Disease";中文检索词为"肌腱,肌腱病,肌腱炎,线粒体,线粒体功能障碍,线粒体疾病".根据纳排标准对检索结果进行筛选,最终纳入62篇文献进行综述.结果与结论:①在临床的肌腱病患者或是肌腱病模型中,普遍存在线粒体功能障碍,主要以活性氧过量产生、超氧化物歧化酶活性降低、嵴杂乱和线粒体数量减少为代表,这说明线粒体将会由于肌腱损伤而发生功能障碍,从而进一步恶化肌腱病,形成恶性循环.②当肌腱尚未损伤或肌腱病尚未发生时,线粒体功能会由于受到内外界各种因素的影响而发生功能障碍,从而诱发肌腱病,这说明正常肌腱将会由于线粒体的功能异常而被损害,发生病变甚至断裂.③机械拉伸应力、晚期糖基化终产物及衰老等内外界因素是导致线粒体功能发生障碍的主要原因,且这些因素将会通过细胞凋亡、炎症和呼吸链损害等分子机制,损害正常肌腱的生物活性与力学性能,诱发肌腱病的发生.④针对分子机制而归纳总结的靶向线粒体治疗方法主要包括线粒体转移/移植、移植及靶向抗氧化剂等.⑤文章主要针对具有肌腱病的临床患者或具有相似造模方式的动物模型,为临床上探讨肌腱病的发病机制以及靶向治疗肌腱病的方法提供新思路,但缺点在于纳入的研究以动物实验为主,需要更多临床试验加以验证.
Mitochondrial dysfunction in tendinopathy:possibility of mitochondria-targeting therapy
BACKGROUND:Various clinical strategies for the treatment of tendinopathy have good short-term effects but poor long-term effects,and some studies have proven that mitochondria are closely related to the occurrence and development of tendinopathy.However,the relationship between mitochondria and tendinopathy and mitochondria-targeting therapeutic strategies for tendinopathy have not been summarized so far,which is not good for specialists and scholars in related fields to understand the recent research situation.OBJECTIVE:To review the existing clinical or preclinical original studies,in order to summarize the relationship between mitochondrial dysfunction and tendinopathy and the mitochondria-targeting methods for the treatment of tendinopathy,and to provide certain prospects for the evaluation and management of mitochondria in tendinopathy in the future.METHODS:The relevant literatures in PubMed,Web of Science,CNKI,WanFang and VIP databases were searched.The search time was from January 2009 to March 2024,and the search terms were"tendinopathy,tendon injuries,tendon,tendons,mitochondria,mitochondria dysfunction,mitochondria disease"both in English and Chinese.According to the exclusion and inclusion criteria,62 articles were finally included for review and analysis.RESULTS AND CONCLUSION:(1)In clinical tendinopathy patients or tendinopathy models,mitochondrial dysfunction is common,mainly represented by excessive production of reactive oxygen species,decreased activity of superoxide dismutase,ridge clutter and decreased number of mitochondria,which indicates that mitochondrial dysfunction will occur due to tendon injury,thus further worsening tendinopathy and forming a vicious cycle.(2)When the tendon has not been injured or tendinopathy has not yet occurred,the mitochondrial function will be affected by various internal and external factors,resulting in tendinopathy.This indicates that the normal tendon will be damaged,lesioned or even ruptured due to the abnormal function of the mitochondria.(3)Mechanical tensile stress,advanced glycosylation end products,aging and other internal and external factors are the main causes of mitochondrial dysfunction,and these factors will damage and weaken the biological activity and mechanical properties of normal tendons through molecular mechanisms such as apoptosis,inflammation and respiratory chain damage,and thereby induce tendinopathy.(4)According to molecular mechanisms,mitochondria-targeting therapies mainly include mitochondrial transfer/transplantation,transplantation,targeted antioxidants,etc.(5)This review mainly aims at clinical patients with tendinopathy or animal models with similar modeling methods,providing a reliable idea for clinical exploration of the pathogenesis of tendinopathy and targeted therapies for tendinopathy.However,the disadvantage is that the included studies are mainly animal experiments,and there is a lack of more clinical trials for verification.