雌激素对肌腱病影响的研究进展

Research progress in the effect of estrogen on tendinopathy

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。

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 receptorβacts more in tendon injury and repair processes,but estrogen receptorαhas not been found to have a major impact on tendon injury.The expression of estrogen receptorβcan 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 receptorβdeficiency regulating interferon regulatory factor 5-chemokine ligand 3 axis,E2 regulating estrogen receptorαand 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 receptorβmainly 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.