中国组织工程研究 ›› 2024, Vol. 28 ›› Issue (32): 5231-5237.doi: 10.12307/2024.501

• 组织构建综述 tissue construction review • 上一篇    下一篇

雌激素对肌腱病影响的研究进展

孙青峰1,白  硕2,张  振3,申  亮4,高蓓瑶5,葛瑞东5   

  1. 1西安交通大学第二附属医院康复医学科,陕西省西安市  710004;2北京市朝阳区太阳宫社区卫生服务中心康复医学科,北京市  100028;3北京大望路急诊抢救医院康复医学科,北京市  100122;4内蒙古赤峰市医院康复医学科,内蒙古自治区赤峰市  024000;5中日友好医院康复医学科,北京市  100029
  • 收稿日期:2023-08-10 接受日期:2023-10-09 出版日期:2024-11-18 发布日期:2023-12-29
  • 通讯作者: 葛瑞东,博士,副主任治疗师,中日友好医院康复医学科,北京市 100029
  • 作者简介:孙青峰,男,2001年生,江西省九江市人,汉族,西安交通大学第二附属医院在读硕士。
  • 基金资助:
    中央高校基本科研业务费专项资金资助课题(校2020064),项目负责人:葛瑞东

Research progress in the effect of estrogen on tendinopathy

Sun Qingfeng1, Bai Shuo2, Zhang Zhen3, Shen Liang4, Gao Beiyao5, Ge Ruidong5   

  1. 1Department of Rehabilitation Medicine, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China; 2Beijing Chaoyang District Taiyanggong Community Health Service Center, Beijing 100028, China; 3Department of Rehabilitation Medicine, Beijing Da Wang Lu Emergency Hospital, Beijing 100122, China; 4Department of Rehabilitation Medicine, Chifeng City Hospital, Chifeng 024000, Inner Mongolia Autonomous Region, China; 5Department of Rehabilitation Medicine, China-Japan Friendship Hospital, Beijing 100029, China 
  • Received:2023-08-10 Accepted:2023-10-09 Online:2024-11-18 Published:2023-12-29
  • Contact: Ge Ruidong, MD, Associate chief therapist, Department of Rehabilitation Medicine, China-Japan Friendship Hospital, Beijing 100029, China
  • About author:Sun Qingfeng, Master candidate, Department of Rehabilitation Medicine, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
  • Supported by:
    Fundamental Research Funds for Central Universities, No. 2020064 (to GRD)

摘要:


文题释义:

雌激素:是促进雌性动物第二性征发育及性器官成熟的物质,由雌性动物卵巢和胎盘分泌产生,分为植物激素(如染料木素)和动物激素(如雌二醇)两种;其作用主要是由雌激素受体介导的,是一种位于内质网的视紫红质样G蛋白偶联受体和两个细胞内激素受体,后者被称为雌激素受体α和β。
肌腱:每一块骨骼肌都分成肌腹和肌腱两部分,肌腱组织由胶原蛋白、成纤维细胞、肌腱细胞和肌腱来源的干细胞组成,Ⅰ型胶原主要由肌腱细胞合成和分泌。肌腱损伤通常是多因素的,可分为肌腱炎(以炎症为特征)和肌腱病(以肌腱结构的退行性改变为特征),且肌腱组织损伤后的自我修复和再生能力较差。


背景:大量的研究发现雌激素与肌腱病具有一定的相关性,但长期以来雌激素在肌腱病中的实验研究成果与总结较少,不方便专科从业者及相关领域学者全面了解研究近况。

目的:综述目前临床或临床前原始研究,以期对雌激素在肌腱病中的作用进行总结,并对未来雌激素在肌腱病中的评估和管理进行一定的展望。
方法:通过计算机对PubMed、Web of Science、中国知网、万方和维普数据库中的相关文献进行检索。检索时间为2008年1月至2023年9月,英文检索词为“Oestrogen, Estrogen, Estrogen receptor, Tendinopathy, Tendonopathy, Sinew, Tendon, Tendons, Myotenositis”;中文检索词为“雌激素,雌激素受体,肌腱病,肌腱,肌腱炎”。依据入选标准对检索结果进行筛选排除,最终纳入60篇文献进行综述分析。

结果与结论:①体内研究表明,雌激素可促进肌腱的合成代谢。也有体外实验证明多种雌激素对肌腱能够起到促进肌腱细胞增殖、减轻炎症反应和细胞凋亡的作用,但实验大都局限于动物模型。②雌激素受体β更多的在肌腱损伤和修复过程起作用,而雌激素受体α暂未发现能够在肌腱损伤过程中产生主要影响。雌激素受体β的表达通过影响脂肪形成、Ⅰ型胶原蛋白的沉积和减少肌腱细胞凋亡来修复肌腱,而其过度表达则可能会促进炎症和血管生成,从而推进炎症进程,在肌腱损伤中发挥作用。③动物研究显示,雌激素缺乏可能会降低肌腱的胶原合成效率,肌腱弹性下降,抑制肌腱的合成代谢,不利于肌腱损伤修复,而正常水平的雌激素可能对肌腱中Ⅰ型胶原合成有刺激作用,促进肌腱细胞增殖和代谢。④目前雌激素在肌腱损伤中作用的分子机制尚未完全阐释,更多实验围绕肌腱胶原合成、细胞增殖凋亡,仅有少量文献研究了雌激素受体β缺陷调控干扰素调节因子5-趋化因子配体3轴、E2调控雌激素受体α和PI-3K-Akt信号通路以及高水平雌二醇降低游离循环胰岛素样生长因子水平3方面的分子机制。⑤包括内源性雌激素和植物雌激素在内的多种雌激素在正常水平时有益于肌腱病的修复,其主要通过雌激素受体β影响脂肪形成、Ⅰ型胶原蛋白的沉积和减少肌腱细胞凋亡发挥作用,这为未来不同亚型雌激素用于在体肌腱病的治疗以及关于雌激素膜性受体种类对肌腱病的影响打下了基础。

https://orcid.org/0009-0000-5325-7131(孙青峰);https://orcid.org/0000-0002-6082-8032(葛瑞东)

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

关键词: 雌激素亚型, 雌激素受体, 雌激素水平, 肌腱病, 肌腱损伤, 肌腱炎, 生物力学特性, 增殖分化, 分子机制, 综述

Abstract: BACKGROUND: Increasing studies have found that estrogen has a certain correlation with tendinopathy, but for a long time, there are few experiments and summaries of estrogen in tendinopathy, which makes it difficult for specialists and scholars in related fields to fully understand the research status.
OBJECTIVE: To summarize the current clinical or preclinical original research, so as to summarize the role of estrogen in tendinosis, and make a certain prospect for the evaluation and management of estrogen in tendinosis in the future.
METHODS: Relevant literature in PubMed, Web of Science, CNKI, WanFang, and VIP databases were searched by computer. Search time was from January 2008 to September 2023. The search terms were “oestrogen, estrogen, estrogen receptor, tendinopathy, tendonopathy, sinew, tendon, tendons, myotenositis” in English and “estrogen, estrogen receptor, tendinosis, tendon, tendinitis” in Chinese. According to the selection criteria, the search results were screened and excluded, and finally 60 documents were included for review and analysis.
RESULTS AND CONCLUSION: In vivo studies have shown that estrogen can promote tendon anabolism. In vitro experiments have also proved that various estrogens can promote the proliferation of tendon cells and reduce inflammation and apoptosis, but most of the experiments are limited to animal models. Estrogen receptor β acts more in tendon injury and repair processes, but estrogen receptor α has not been found to have a major impact on tendon injury. The expression of estrogen receptor β can repair the tendon by affecting the formation of fat, the deposition of type I collagen and reducing the apoptosis of tendon cells, while its over-expression may promote inflammation and angiogenesis, thus promoting the inflammatory process and playing a role in tendon injury. Animal studies have shown that estrogen deficiency may reduce the synthesis efficiency of collagen in the tendon, decrease the elasticity of tendon, inhibit the synthesis and metabolism of the tendon, which is not conducive to the repair of tendon injury, while normal level of estrogen may stimulate the synthesis of type I collagen in tendon and promote the proliferation and metabolism of tendon cells. At present, the molecular mechanism of estrogen in tendon injury has not been fully explained. More experiments focus on tendon collagen synthesis, cell proliferation and apoptosis. Only a few documents have studied the molecular mechanisms of estrogen receptor β deficiency regulating interferon regulatory factor 5-chemokine ligand 3 axis, E2 regulating estrogen receptor α and PI-3K-Akt signaling pathways, and high levels of estradiol reducing the level of free-circulating insulin-like growth factor. Various estrogens, including endogenous estrogens and phytoestrogens, are beneficial to the repair of tendinopathy at normal levels, and estrogen receptor β mainly affects the formation of fat, the deposition of type I collagen and the reduction of apoptosis of tendon cells through, which lays a foundation for the future treatment of tendinopathy with different subtypes of estrogens in vivo and the influence of estrogen membrane receptors on tendinopathy.

Key words: estrogen subtype, estrogen receptor, estrogen level, tendinopathy, tendon injury, tendinitis, biomechanical characteristics, proliferation and differentiation, molecular mechanism, review

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