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医学中的昼夜节律机制
Circadian Mechanisms in Medicine


Ravi Allada ... 其他 • 2021.02.11
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除决定睡眠-觉醒周期和认知功能(例如学习和记忆)之外,生物钟还决定了生理上的几乎所有昼夜节律周期,如血压、心率、激素水平、呼吸、运动能力和凝血的日常变化。许多病理状况发生在一天中的特定时间,这表明昼夜节律促发疾病(图1)。生物钟系统的核心功能是根据预计的昼夜循环驱动能量的获取和利用。在分子水平理解昼夜节律可开启治疗领域的新洞见,有助于我们预防和治疗疾病。

 

图1. 昼夜节律网络和地球物理时间

生物钟的分子回路由脑内自我调节的24小时转录回路编码,生物钟将睡眠-觉醒周期和进食周期与地球自转同步。生物钟几乎存在于体内所有组织,构成了可预测日常不同环境状况的计时器网络。分子回路在各界生物中演化而来,该回路为光敏物种提供了增强生物能循环,并确保其免受日光对DNA所造成损伤的机制。BMAL1表示脑和肌肉Arnt样蛋白1(brain and muscle Arnt-like protein 1),CLOCK表示昼夜运动输出周期kaput(circadian locomotor output cycles kaput),CRY表示隐花色素,PER表示period,RORE表示视黄酸相关孤儿受体(ROR)反应元件,SCN表示视交叉上核。

 

生理上的昼夜节律


昼夜节律即使在恒定不变的环境下也以大约24小时(circa diem,大约一天)的周期持续存在(参见方框中的简要总结)。光照使生物钟与地球的24小时自转同步(图1)。根据光暗循环判断时间的最早生命形式是光合细菌。生物钟的演化与30亿年前的氧气大增同时发生,从根本上将昼夜节律与生氧呼吸联系在一起1。生物钟可能是在四界生物中分别独立演化而来,这提示生物钟对于物种的健康和生存至关重要1





作者信息

Ravi Allada, M.D., and Joseph Bass, M.D., Ph.D.
From the Department of Neurobiology, Northwestern University, Evanston (R.A.), and the Department of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, Chicago (J.B.) — both in Illinois. Address reprint requests to Dr. Bass at the Department of Medicine, Northwestern University, 303 E. Superior St., Lurie 7-107, Chicago, IL 60611, or at j-bass@northwestern.edu.

 

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