昼夜节律与心脏代谢研究进展

昼夜节律使有机体内部生物功能与环境昼夜周期变化一致,生物体内几乎所有重要生理过程均受其调控,包括心脏代谢。昼夜节律的紊乱也会导致心脏代谢节律的紊乱,引发一系列病理生理改变。现综述昼夜节律与心脏代谢的研究进展,阐述昼夜节律对心脏代谢的调控机制。     

昼夜节律参与急性心肌梗死发生的机制及其对患者预后影响的研究进展

流行病学证据显示急性心肌梗死的发生在清晨达到高峰,表现为昼夜节律性,可能是由内部节律因素和外界环境因素共同作用所致,但具体机制尚不明确.急性心肌梗死作为危重症之一,其产生的不良预后给患者及家属带来重大的生活负担.昼夜节律与急性心肌梗死预后的关系目前仍有争议,两者关系的探讨有利于揭露昼夜节律对急性心肌梗死预后影响的重要性...     

昼夜节律调节心律失常的机制及治疗药物的研究进展

昼夜节律是一种正常生理节律,调控着机体的生理机能以适应外界环境的变化,对包括心脏在内的机体众多生理和病理过程发挥重要作用,其紊乱易导致心律失常的发生。现综述昼夜节律调节心律失常发生的分子基础及机制,归纳了伊伐布雷定、β₁受体阻滞剂、莫雷西嗪、胺碘酮等治疗药物通过改变昼夜节律基因,发挥抗心律失常作用的机制,旨在为心律失常的预防、治疗及术后康复提供新的思路。     

帕金森病与昼夜节律异常

机体的许多生理活动包括内分泌、代谢、免疫等均受昼夜节律的调控。昼夜节律异常与多种疾病有关,如肿瘤、 肥胖、糖尿病及情感障碍等, 其中也包括神经退行性疾病。帕金森病(PD) 是第二常见的神经退行性疾病,仅次于阿 尔茨海默病,其典型临床表现包括静止性震颤、肌强直、运动迟缓和姿势步态异常,同时也伴随许多非运动症状。昼 夜节律异常是其最常见的非运动症状之一,可发生于运动症状出现之前,亦可伴随整个病程,给患者及照料者的生 活质量造成了沉重的负担。文章将对PD 昼夜节律异常表现、生物学标志物变化及现有干预措施进行简要介绍。     

载脂蛋白E基因敲除小鼠钟基因、凋亡相关基因及动脉粥样硬化相关基因表达节律的改变

目的急性心肌梗死是动脉粥样硬化的终末病变,发病具有昼夜节律——早晨高发,这提示昼夜节律生物钟参与了这一病理过程。因此我们检测了动脉粥样硬化发展过程中生物钟基因、凋亡相关基因以及动脉粥样硬化相关基因的表达变化。方法应用载脂蛋白E基因敲除(载脂蛋白E-/-)小鼠建立动     

原发性高血压患者血压昼夜节律、血压变异性与动脉粥样硬化的相关性研究

目的:探讨原发性高血压患者的血压昼夜节律、血压变异性与动脉粥样硬化的关系。方法:入选原发性高血压患者120例,行24 h动态血压监测,根据血压昼夜节律分为杓型组(n=22)、非杓型组(n=36)和反杓型组(n=62)。分析比较3组的血压变异性、冠心病发生率及颈动脉斑块检出率。结果:反杓型组的24 h收缩压标准差(24hSSD)、24 h舒张压标准差(24hDSD)、白昼收缩压标准差(dSSD)、白昼舒张压标准差(dDSD)、24 h收缩压变异系数(24hSBP-CV)、夜间收缩压变异系数(nSBP-CV)均低于杓型组;反杓型组的24hDSD、dDSD、24hDBP-CV低于非勺型组;反杓型组冠心病发生率及颈动脉斑块检出率较杓型组明显升高(P均<0.05)。结论:原发性高血压患者血压昼夜节律异常对动脉粥样硬化进展可能有促进作用。     

鱼油对动脉粥样硬化形成的影响

本文回顾了近年有关鱼油廿碳五烯酸(EPA)和廿二碳六烯酸(DHA)对动脉粥样硬化病变的影响及作用机理的研究。实验研究表明,鱼油可以减轻或抑制实验性动脉粥样硬化的发生,因此,在动脉粥样硬化及冠心病的预防和治疗方面可能具有重要意义。     

"生物钟对骨代谢影响"的研究进展

生物钟普遍存在于各种生物体,参与调节机体多种生理过程和行为,以保持与外部环境时间的协调,维持内环境稳态.近年来许多临床和基础研究表明,骨代谢疾病的发生、发展与生物钟改变导致的机体昼夜节律紊乱密切相关.此外,部分患者接受抗骨质疏松药物治疗的时间窗口差异,可不同程度影响治疗效果.本文梳理生物钟与骨代谢相关性研究文献和数据,...     

心律失常发生的昼夜节律

研究表明,心脏电生理参数、阵发性室上性心动过速、心房颤动、室性心律失常的发生都存在昼夜节律.心律失常发生的昼夜节律可能与心脏外周时钟,以及自主神经的调节的程度相关.     

细胞信号转导通路与动脉粥样硬化的研究进展

动脉粥样硬化(atherosclerosis,AS)是由单核/淋巴细胞黏附并激活内皮细胞(EC)而开启的由多种原因导致的疾病[1],是冠状动脉疾病、周围动脉疾病、脑梗死等血管性疾病的病理基础.     

动脉粥样硬化危险因素衰老、肥胖、生物钟紊乱与核糖体新生的研究进展

动脉粥样硬化是心脑血管疾病的主要原因,可能由吸烟、高血压、衰老、肥胖、生物钟紊乱等多因素导致。核糖体作为蛋白质合成的分子机器,维持细胞内蛋白质稳态。文章聚焦于衰老、肥胖和生物钟紊乱对动脉粥样硬化的影响,以及与核糖体新生的关系,为动脉粥样硬化的机制研究和防治提供理论支持。     

Disruption of circadian rhythm by alternating light-dark cycles aggravates atherosclerosis development in APOE*3-Leiden.CETP mice

Disruption of circadian rhythm by means of shift work has been associated with cardiovascular disease in humans. However, causality and underlying mechanisms have not yet been established. In this study, we exposed hyperlipidemic APOE*3-Leiden.CETP mice to either regular light-dark cycles, weekly 6 hours phase advances or delays, or weekly alternating light-dark cycles (12 hours shifts), as a well-established model for shift work. We found that mice exposed to 15 weeks of alternating light-dark cycles displayed a striking increase in atherosclerosis, with an approximately twofold increase in lesion size and severity, while mice exposed to phase advances and delays showed a milder circadian disruption and no significant effect on atherosclerosis development. We observed a higher lesion macrophage content in mice exposed to alternating light-dark cycles without obvious changes in plasma lipids, suggesting involvement of the immune system. Moreover, while no changes in the number or activation status of circulating monocytes and other immune cells were observed, we identified increased markers for inflammation, oxidative stress, and chemoattraction in the vessel wall. Altogether, this is the first study to show that circadian disruption by shifting light-dark cycles directly aggravates atherosclerosis development.     

Peripheral circadian clock for the cuticle deposition rhythm in Drosophila melanogaster

Insect endocuticle thickens after adult emergence by daily alternating deposition of two chitin layers with different orientation. Although the cuticle deposition rhythm is known to be controlled by a circadian clock in many insects, the site of the driving clock, the photoreceptor for entrainment, and the oscillatory mechanism remain elusive. Here, we show that the cuticle deposition rhythm is regulated by a peripheral oscillator in the epidermis in Drosophila melanogaster. Free-running and entrainment experiments in vitro reveal that the oscillator for the cuticle deposition rhythm is independent of the central clock in the brain driving the locomotor rhythms. The cuticle deposition rhythm is absent in null and dominant-negative mutants of clock genes (i.e., period, timeless, cycle, and Clock), indicating that this oscillator is composed of the same clock genes as the central clock. Entrainment experiments with monochromatic light-dark cycles and cry(b) flies reveal that a blue light-absorbing photoreceptor, cryptochrome (CRY), acts as a photoreceptor pigment for the entrainment of the cuticle deposition rhythm. Unlike other peripheral rhythms in D. melanogaster, the cuticle deposition rhythm persisted in cry(b) and cry(OUT) mutant flies, indicating that CRY does not play a core role in the rhythm generation in the epidermal oscillator.     

昼夜节律在病毒感染中的作用

昼夜节律是由内源性时钟调节的多个生物过程的日常振荡,调控机体的各种生理变化.节律紊乱会导致多种疾病的发生,包括代谢综合征和癌症等.最近将昼夜节律系统作用研究扩展到了感染的调控,宿主与病原体的相互作用以及由此产生的疾病结局.深入了解昼夜节律系统在调节病毒感染中的作用将为病毒性传染病的致病机理、抗病毒治疗、疫苗研发等提供新的思路.本文就昼夜节律与病毒感染的相互作用进行综述,包括昼夜节律如何影响病毒感染以及病毒如何调节节律以促进自身复制的关键发现,突出昼夜节律的重要性.     

血压昼夜节律异常对不同亚型急性缺血性脑卒中影响的研究

目的探讨高血压患者血压昼夜节律异常对不同亚型急性缺血性脑卒中的影响。方法参照改良TOAST分型标准,将97例伴高血压的急性缺血性脑卒中患者分为动脉粥样硬化血栓形成(arterothrombosis,AT)组66例和小动脉病变(small artery disease,SAD)组31例,并进行24h动态血压监测。比较2组间24h、昼间和夜间的血压水平、晨峰血压及血压昼夜节律的变化。结果 AT组夜间收缩压明显高于SAD组[(133.86±18.17)mm Hg vs(124.42±16.06)mm Hg,1mm Hg=0.133kPa,P<0.05];AT组血压昼夜节律消失比例明显高于SAD组(84.8%vs 64.5%,P<0.05);2组晨峰血压发生率比较,差异无统计学意义(37.9%vs 19.4%,P>0.05)。结论血压昼夜节律消失和夜间血压水平升高与AT型缺血性脑卒中的发生有关。     

Ventral lateral and DN1 clock neurons mediate distinct properties of male sex drive rhythm in Drosophila

Male sex drive rhythm (MSDR) in Drosophila is a circadian behavior only observed in the social context of male-female pairs. In the presence of a female, males exhibit long periods of courtship activity with a pronounced rest phase at dusk, although isolated males exhibit an activity peak at dusk. The molecular mechanisms regulating the switch between these activity patterns are unknown. Here, we genetically manipulate the molecular clock in different subsets of neurons and find that proper oscillation of the molecular clock in ventral lateral neurons is essential for MSDR. These neurons express pigment-dispersing factor, the lack of which disrupts MSDR. Furthermore, we show that a cluster of dorsal neurons (DN1s) requires the molecular clock to synchronize the trough phase at dusk in MSDR and to establish the evening peak in single fly locomotor rhythm (SLR). Finally, we provide evidence that DN1s exert their roles in MSDR and SLR via distinct signaling pathways.     

Control of skin cancer by the circadian rhythm

Skin cancer is the most common form of cancer in the United States. The main cause of this cancer is DNA damage induced by the UV component of sunlight. In humans and mice, UV damage is removed by the nucleotide excision repair system. Here, we report that a rate-limiting subunit of excision repair, the xeroderma pigmentosum group A (XPA) protein, and the excision repair rate exhibit daily rhythmicity in mouse skin, with a minimum in the morning and a maximum in the afternoon/evening. In parallel with the rhythmicity of repair rate, we find that mice exposed to UV radiation (UVR) at 4:00 AM display a decreased latency and about a fivefold increased multiplicity of skin cancer (invasive squamous cell carcinoma) than mice exposed to UVR at 4:00 PM. We conclude that time of day of exposure to UVR is a contributing factor to its carcinogenicity in mice, and possibly in humans.     

Melatonin resynchronizes dysregulated circadian rhythm circuitry in human prostate cancer cells

Abstract: Prostate cancer (PCa) is a major age‐related malignancy as increasing age correlates with increased risk for developing this neoplasm. Similarly, alterations in circadian rhythms have also been associated with the aging population and cancer risk. The pineal hormone melatonin is known to regulate circadian rhythms, which is under the control of a core set of genes: Period 1, 2, 3 (Per 1–3); Cryptochrome 1, 2 (Cry 1, 2); Clock, and Bmal 1, 2. Melatonin levels have been shown to decrease in patients with cancer and exogenous melatonin exhibits antiproliferative effects against certain cancers. In this study, we challenged the hypothesis that melatonin imparts antiproliferative effects in prostate cancer via resynchronization of deregulated core clock circuitry. We found that Clock and Per2 protein levels were downregulated whereas Bmal1 protein levels were upregulated in PCa cells, compared to normal prostate cells. Additionally, employing automated quantitative analysis of a microarray containing human tissues, we found that compared to benign tissues, Clock and Per2 levels were downregulated, whereas Bmal1 levels were upregulated in PCa and other proliferative prostatic conditions. Overexpression of Per2 was found to result in a significant loss of PCa cell growth and viability. Interestingly, melatonin treatment resulted in an increase in Per2 and Clock and a reduction in Bmal1 in PCa cells. Further, melatonin treatment resulted in a resynchronization of oscillatory circadian rhythm genes (Dbp and Per2). Our data support our hypothesis and suggest that melatonin should be thoroughly investigated as an agent for the management of PCa and other age‐related malignancies.     

234例原发性高血压患者血压昼夜节律分析

目的　探讨原发性高血压患者血压昼夜节律曲线类型和年龄、性别、血压水平、眼底小动脉、肾功能及血管内皮功能之间的关系。方法　选择初诊原发性高血压患者 2 34例 ,根据动态血压检测结果将昼夜节律曲线分为反杓型、非杓型、杓型和超杓型 4组。检测 2 4h动态血压、眼底、血液生化及血管内皮功能。结果　不同血压曲线类型组之间收缩压、舒张压、脉压、年龄以及各曲线类型组之间单纯收缩期高血压的分布有显著差异 ,其中 ,反杓型组和非杓型组的年龄显著大于杓型组 ,非杓型组中单纯收缩期高血压的比例高于杓型组 ;而不同血压曲线类型组之间性别、眼底动脉硬化程度、尿素氮、血肌酐、内皮素及一氧化氮无显著性差异。结论　 4种血压节律曲线类型与年龄明显相关 ,而与性别、眼底小动脉硬化程度、肾功能、血管内皮功能之间无明显相关关系。     

大鼠心脏自噬昼夜节律的老年化改变研究

目的探讨大鼠心脏自噬昼夜节律的老年化改变及可能机制。方法随机选取健康雄性SD大鼠48只,其中6月龄大鼠24只(青年组)和26月龄大鼠24只(老年组)。观察大鼠昼夜活动习性,分别在03:00,06:00,09:00,12:00,15:00,18:00,21:00,24:00各时间点收集心脏样本,运用冷冻切片免疫荧光染色结合激光扫描共聚焦成像技术、亚细胞结构细胞核-细胞质分离技术和免疫印迹技术检测心脏自噬规律及可能调控机制。结果青年组大鼠昼伏夜出,自噬昼夜节律曲线明显,其中18:00 LC3-Ⅰ转化LC3-Ⅱ明显高于12:00,而在15:00细胞核C/EBPβ表达明显高于18:00(P<0.05);而老年组大鼠夜间及昼间均嗜睡,LC3-Ⅰ转化LC3-Ⅱ和细胞核C/EBPβ昼夜无节律性变化。结论衰老改变心脏自噬的昼夜节律,核转录因子C/EBPβ参与其调控。