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模拟轮班工作引起的循环节障碍通过编排BMAL1和GSDMD介导的烧会加剧牙周炎

Yazheng Wang^1,2, Rui Li¹, Qingyuan Ye³

¹State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Department of Periodontology, School of Stomatology, the Fourth Military Medical University, Xi'an, China.

International journal of oral science

|February 25, 2025

概括

轮班工作扰乱昼夜节律,通过降低大脑和肌肉ARNT样蛋白1 (BMAL1) 的调节,加剧牙周炎,并激活Gasdermin D (GSDMD) 介导的热. 恢复BMAL1水平可以减轻这种损伤.

科学领域:

时间生物学时间生物学
牙周病学牙周病学
疾病的分子机制.

背景情况:

轮班工作影响全球20%-30%的劳动力,导致昼夜干扰.
轮班工作的循环节障碍与牙周炎风险增加有关.
连接轮班工作,昼夜干扰和牙周炎的确切机制尚未完全理解.

研究的目的:

通过模拟轮班工作模型,研究昼夜干扰在牙周炎进展中的作用.
阐明分子通路,包括核心昼夜蛋白和炎症反应,涉及轮班工作加剧的牙周炎.

主要方法:

利用模拟轮班工作模型与受控的光暗周期.
进行RNA测序和体外实验以确定关键分子参与者.
研究了大脑和肌肉ARNT样蛋白1 (BMAL1),Gasdermin D (GSDMD) 介导的热和NOD样受体蛋白3 (NLRP3) 炎症体信号传递之间的相互作用.

主要成果:

与轮班工作相关的昼夜干扰加剧了实验性牙周炎.
降低BMAL1的调节和激活GSDMD介导的烧被确定为关键的致病因素.
发现BMAL1通过NR1D1抑制NLRP3炎症酶信号传递,并抑制Gsdmd转录,从而减少热.

结论:

轮班工作条件下的循环节障碍通过增加由于BMAL1下调而导致的GSDMD活动而加剧牙周破坏.
通过昼夜恢复或SR8278注射恢复BMAL1水平,通过减少GSDMD介导的烧,减轻了牙周炎的严重程度.
这些发现突出了与昼夜干扰相关的牙周炎的潜在治疗点.

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