几十年前，科学家们就知道心脏病和中风在清晨发作频度最高。宾西法尼亚大学医学院研究人员进行的一项最新的研究首次找到了人体内在分子钟控制血压机制的证据，为改变人体血压和降低清晨心脏病发作风险提供了可能。该研究成果在线发表于《美国国家科学院院刊》（PNAS）上。
分子钟是一系列位于大脑分散区域的复杂基因，这些区域紧密调节着人体行为、温度和新陈代谢的生理节奏。
心脏病发作风险与血压的变化息息相关，而人体血压有24小时周期变化的生理节奏，高血压患者血压的变化幅度更大。然而，这种情况到底是分子钟造成的还是仅仅反映出分子钟与被唤醒、匆忙穿衣上班等环境压力的关系，科学界一直存在争议。论文的首席作者Annie M. Curtis表示，“该研究为统一血压变化与分子钟关系的两种理论提供了依据。”
研究人员通过破坏实验小鼠的主要分子钟基因功能，发现小鼠的血压和生理节奏发生了明显变化。此外，与儿茶酚胺（Catecholamines）产生和分解相关的基因也由分子钟控制。儿茶酚胺是哺乳动物在压力下产生的一类激素，浓度也有每日变化规律，且会随着压力的增大而上升。
该项研究的最大成就在于，儿茶酚胺浓度和血压的上升都与压力产生的时间有关。而对于人类来说，最大的变化发生在清晨时分。同时，研究显示，不论压力何时在分子钟周期起作用，去除核心分子钟基因都将会完全消除儿茶酚胺和血压对环境压力的响应。
该研究结果将有助于通过药物干扰分子钟来减少高血压患者清晨心脏病发作的风险。
英文原文摘要：
Circadian variation of blood pressure and the vascular response to asynchronous stress
Anne M. Curtis, Yan Cheng, Shiv Kapoor, Dermot Reilly, Tom S. Price, and Garret A. FitzGerald*
Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, 153 Johnson Pavilion, Philadelphia, PA 19104
Communicated by Ronald M. Evans, The Salk Institute for Biological Studies, San Diego, CA, January 2, 2007 (received for review July 7, 2006)
Abstract
The diurnal variation in the incidence of myocardial infarction and stroke may reflect an influence of the molecular clock and/or the time dependence of exposure to environmental stress. The circadian variation in blood pressure and heart rate is disrupted in mice, Bmal1–/–, Clockmut, and Npas2mut, in which core clock genes are deleted or mutated. Although Bmal1 deletion abolishes the 24-h frequency in cardiovascular rhythms, a shorter ultradian rhythm remains. Sympathoadrenal function is disrupted in these mice, which reflects control of enzymes relevant to both synthesis (phenylethanolamine N-methyl transferase) and disposition (monoamine oxidase B and catechol-O-methyl transferase) of catecholamines by the clock. Both timing and disruption or mutation of clock genes modulate the magnitude of both the sympathoadrenal and pressor but not the adrenocortical response to stress. Despite diurnal variation of catecholamines and corticosteroids, they are regulated differentially by the molecular clock. Furthermore, the clock may influence the time-dependent incidence of cardiovascular events by controlling the integration of selective asynchronous stress responses with an underlying circadian rhythm in cardiovascular function.
