冷暴露后导致中风发作的过程

H. Morimoto
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摘要

背景:众所周知,随着气温的下降,中风的死亡率在更大程度上增加。环境因素可能在引发中风发作中起主要作用。在寒冷暴露和中风发作之间有一个延迟。这一事实可能反映了冷暴露后的复杂机制。然而,冷暴露后的精确过程并没有很好的记录。本文的目的是研究寒冷暴露后影响人体健康的过程,探讨天气和基因表达的变化。方法和研究结果:我们使用日本名古屋市2002年至2005年期间提供的患者救护车数据。这些数据包括每天由救护车送往医院,然后在医院被诊断为中风或脑梗死的所有年龄段患者的数量。我们还使用了从国家生物技术信息中心(NCBI)维护的基因表达综合数据库GEO (gene expression omnibus)中提取的基因表达数据。该方法基于平均温度和相对湿度两个变量平面上的随机游走。我们提取了与冷暴露导致中风发作的路径相对应的随机行走,并对冷却和再加热随机行走的特征进行了分类。在这些随机行走中观察到相对湿度的增加,并提示炎症系统的重要性。为了探讨冷暴露后的可能机制,我们检查了GEO数据库中的基因表达数据,发现细胞因子相关基因,特别是白细胞介素6信号传感器IL6st和白细胞介素受体IL17的表达增加。这些白细胞介素在炎症反应中起重要作用。结论:细胞因子基因表达与气象因子中“冷暖随机游走”的对应关系,将提供一种连接天气与疾病的方案,为脑卒中预防研究提供新的途径。
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Processes After Cold Exposure Leading to the Onset of Stroke
Background: The mortality from stroke is known to increase to a greater extent with the fall of temperature. Environmental factors may play a major role in triggering of the onset of stroke. There is a delay between cold exposure and the onset of stroke. This fact may reflect the complex mechanism after cold exposure. However, a precise process after cold exposure is not well documented. The purpose of this paper is to study the processes after cold exposure that affect human health, exploring the changes in both weather and gene expression. Methods and findings: We used ambulance data of patients provided by the city of Nagoya in Japan during a period from 2002 to 2005. The data included the daily number of patients of all ages, who were first transported by ambulance to a hospital and then diagnosed at the hospital with stroke or cerebral infarction. We used also gene expression data extracted from the database GEO (gene expression omnibus) maintained by The National Center for Biotechnology Information (NCBI). The method is based on random walks in the plane of two variables, mean temperature and relative humidity. We extracted random walks that correspond to paths after cold exposure leading to the onset of stroke and classified the characteristic feature of cooling and rewarming random walks. The increase of relative humidity was observed during these random walks, and suggested the importance of inflammatory system. To discuss a possible mechanism after cold exposure, we examined the gene expression data among the database GEO, and found the increase of cytokine-related genes, especially interleukin 6 signal transducer IL6st and interleukin receptors of IL17. These interleukins play an important role in inflammatory responses. Conclusion: The correspondence between the gene expressions of cytokines and "cooling and rewarming random walks" in the meteorological factors will provide a scheme that connects weather and disease, and will provide novel avenues for research in the prevention of stroke.
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