为什么早上身体会僵硬:晚上睡觉身体在抑制炎症
2016/08/09
新的研究描述了人体生物钟产生的一种蛋白质,在夜晚积极地抑制四肢的炎症通路。

发表在FASEB杂志上的新研究,描述了人体生物钟产生的一种蛋白质,在夜晚积极地抑制炎症通路。这种蛋白质称为隐花色素,已被证实有抗炎作用,并且有望用于炎症治疗,例如关节炎。

“通过了解生物钟蛋白质如何调节炎症,我们就可以利用这方面的知识开发新的治疗方法。”英国曼彻斯特大学人类发展研究所的内分泌和糖尿病研究中心的研究员Julie Gibbs博士说,“此外,通过调节药物治疗有效时间,我们可以增加药效。”

吉布斯和他的同事们从健康小鼠或者人类的关节组织中收集细胞。这些细胞称为纤维细胞样滑膜细胞,在炎症性关节炎病理学研究中是十分重要的研究对象。这些细胞有一个24小时的循环,当这个循环因为隐花色素移除而被破坏时,炎症反应加重了。这表明,隐花色素基因产物具有显著抗炎作用。为了验证这一假设,研究人员设计了一类用来激活蛋白质的药物来确认是否能够对抗炎症,结果表明的确有效。

“这项研究告诉我们,炎症通常被认为是慢性的,难以治愈的。可事实上,这个研究中,在大脑控制生理节奏的视交叉上核神经的影响下,炎症变得不那么可怕。这个研究的临床意义是深远的。”FASEB杂志的主编Thoru Pederson博士说。

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  • The circadian clock regulates inflammatory arthritis

    There is strong diurnal variation in the symptoms and severity of chronic inflammatory diseases, such as rheumatoid arthritis. In addition, disruption of the circadian clock is an aggravating factor associated with a range of human inflammatory diseases. To investigate mechanistic links between the biological clock and pathways underlying inflammatory arthritis, mice were administered collagen (or saline as a control) to induce arthritis. The treatment provoked an inflammatory response within the limbs, which showed robust daily variation in paw swelling and inflammatory cytokine expression. Inflammatory markers were significantly repressed during the dark phase. Further work demonstrated an active molecular clock within the inflamed limbs and highlighted the resident inflammatory cells, fibroblast-like synoviocytes (FLSs), as a potential source of the rhythmic inflammatory signal. Exposure of mice to constant light disrupted the clock in peripheral tissues, causing loss of the nighttime repression of local inflammation. Finally, the results show that the core clock proteins CRYPTOCHROMES 1 and 2 repressed inflammation within the FLSs, and provide novel evidence that a CRYPTOCHROME activator has anti-inflammatory properties in human cells. We conclude that under chronic inflammatory conditions, the clock actively represses inflammatory pathways during the dark phase. This interaction has exciting potential as a therapeutic avenue for treatment of inflammatory disease.—Hand, L. E., Hopwood, T. W., Dickson, S. H., Walker, A. L., Loudon, A. S. I., Ray D. W., Bechtold, D. A., Gibbs, J. E. The circadian clock regulates inflammatory arthritis.

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