幾十年前,，科學(xué)家們就知道心臟病和中風(fēng)在清晨發(fā)作頻度最高,。賓西法尼亞大學(xué)醫(yī)學(xué)院研究人員進(jìn)行的一項(xiàng)最新的研究首次找到了人體內(nèi)在分子鐘控制血壓機(jī)制的證據(jù),，為改變?nèi)梭w血壓和降低清晨心臟病發(fā)作風(fēng)險(xiǎn)提供了可能,。該研究成果在線發(fā)表于《美國(guó)國(guó)家科學(xué)院院刊》（PNAS）上,。
分子鐘是一系列位于大腦分散區(qū)域的復(fù)雜基因,，這些區(qū)域緊密調(diào)節(jié)著人體行為、溫度和新陳代謝的生理節(jié)奏。
心臟病發(fā)作風(fēng)險(xiǎn)與血壓的變化息息相關(guān),，而人體血壓有24小時(shí)周期變化的生理節(jié)奏,，高血壓患者血壓的變化幅度更大。然而,，這種情況到底是分子鐘造成的還是僅僅反映出分子鐘與被喚醒,、匆忙穿衣上班等環(huán)境壓力的關(guān)系，科學(xué)界一直存在爭(zhēng)議,。論文的首席作者Annie M. Curtis表示,，“該研究為統(tǒng)一血壓變化與分子鐘關(guān)系的兩種理論提供了依據(jù)。”
研究人員通過(guò)破壞實(shí)驗(yàn)小鼠的主要分子鐘基因功能,，發(fā)現(xiàn)小鼠的血壓和生理節(jié)奏發(fā)生了明顯變化,。此外，與兒茶酚胺（Catecholamines）產(chǎn)生和分解相關(guān)的基因也由分子鐘控制,。兒茶酚胺是哺乳動(dòng)物在壓力下產(chǎn)生的一類激素,，濃度也有每日變化規(guī)律，且會(huì)隨著壓力的增大而上升,。
該項(xiàng)研究的最大成就在于,，兒茶酚胺濃度和血壓的上升都與壓力產(chǎn)生的時(shí)間有關(guān)。而對(duì)于人類來(lái)說(shuō),，最大的變化發(fā)生在清晨時(shí)分。同時(shí),，研究顯示,，不論壓力何時(shí)在分子鐘周期起作用，去除核心分子鐘基因都將會(huì)完全消除兒茶酚胺和血壓對(duì)環(huán)境壓力的響應(yīng),。
該研究結(jié)果將有助于通過(guò)藥物干擾分子鐘來(lái)減少高血壓患者清晨心臟病發(fā)作的風(fēng)險(xiǎn),。
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.
