TASK-1在SD大鼠呼吸中枢的表达及其与睡眠呼吸暂停现象之间的关系

发布时间：2018-03-26 12:15

本文选题：钾离子通道　切入点：TASK-1　出处：《河北医科大学》2005年博士论文

【摘要】：中枢化学感受器(central chemoreceptors, CCRs)在快速调节机体酸碱平衡以及内环境稳定的过程中发挥着重要作用。已发现对化学性刺激(H+/CO_2)敏感的部位主要位于脑干背侧和腹侧以及中缝核和蓝斑等一些神经核团。但是脑脊液中的H+/CO2的变化是以何种方式被这些核团感知的?它们又怎样引起了中枢呼吸冲动发放的改变?这一系列变化的发生机理仍然是未解之谜。早在1989 年就有学者提出,对化学刺激敏感的神经元的去极化反应是由于在静息状态下开放的K~+通道被抑制所导致的。此种存在于细胞膜上的K~+通道的电流变化可能是CCRs 对酸碱刺激做出反应的分子基础。近年发现的两孔道K~+通道TASK-1(TWIK-related acid-sensitive K~+ channel-1;TWIK, for tandem P domains in a weak inwardly rectifying K+)就是一种对生理状态下细胞外液pH 值敏感的,且在静息状态下开放的外向整流型K~+通道。这种离子通道在脑干多种神经元上都有表达,并对五羟色胺(5-HT)、去甲肾上腺素(NE)、P 物质等一些与呼吸调节相关的神经递质敏感。因此推测TASK-1 可能是存在于中枢的化学感受器分子,当细胞外pH 值降低时,可通过增加细胞的兴奋性而使呼吸活动增强。睡眠呼吸暂停综合征(sleep apnea syndrome, SAS)是一种严重危害人类身体健康的疾病。目前研究发现呼吸暂停的发生与中枢呼吸调控不稳有关,而且这种调控不稳可能来自于中枢化学感受器敏感性的异常。联系TASK-1 的通道特性以及在中枢一些特定神经元上的存在,我们推测TASK-1 的表达量及功能的变化可能参与了SAS 的发病。因此,本次研究工作将首先系统观察TASK-1 mRNA 在脑干呼吸相关神经元上的表达情况并观察TASK-1 的通道电流特性,从解剖学分布和电生理学特性上初步判断TASK-1 与中枢呼吸调控之间可能存在的关系。然后通过分析TASK-1 mRNA 在低位脑干上表达量与Sprague-Dawley (SD)大鼠睡眠呼吸暂停指数之间的相关性,探讨TASK-1 与睡眠呼吸暂停之间
[Abstract]:Central chemoreceptor (CCRs) plays an important role in the rapid regulation of acid-base balance and stability of the internal environment. It has been found that the sites sensitive to chemical stimuli are mainly located in the dorsal and ventral side of the brain stem. Some neuronuclei, such as raphe nuclei and locus coeruleus, but in what way are changes in H / CO _ 2 in cerebrospinal fluid perceived by these nuclei? How do they cause changes in central respiratory impulses? The mechanism of this series of changes is still a mystery. As early as 1989 years ago, some scholars suggested, The depolarization of chemically sensitive neurons is due to the inhibition of open K ~ channels in the resting state. This current change of K ~ channel in the cell membrane may be a reaction of CCRs to the acid-base stimulation. In recent years, the two-channel K ~ channel TASK-1(TWIK-related acid-sensitive K ~ channel-1, for tandem P domains in a weak inwardly rectifying K) is sensitive to the pH value of extracellular fluid in physiological state. And open outward rectifier K ~ channels at rest, which are expressed in a variety of neurons in the brain stem. Some neurotransmitters related to respiratory regulation, such as serotonin 5-HT, norepinephrine and so on, are sensitive to respiratory regulation. Therefore, we speculate that TASK-1 may be a chemoreceptor molecule in the central nervous system, when the extracellular pH decreases, Respiratory activity can be enhanced by increasing cell excitability. Sleep apnea syndrome (Sass) is a disease that seriously endangers human health. Recent studies have found that apnea is associated with unstable central respiratory regulation. Furthermore, this regulatory instability may be due to the abnormal sensitivity of central chemosensors. In connection with the channel characteristics of TASK-1 and the presence of specific neurons in the central nervous system, we speculate that the changes in the expression and function of TASK-1 may be involved in the pathogenesis of SAS. Therefore, the expression of TASK-1 mRNA in brain stem respiratory related neurons and the channel current characteristics of TASK-1 were observed systematically in this study. The possible relationship between TASK-1 and central respiratory regulation was preliminarily determined in terms of anatomical distribution and electrophysiological characteristics, and then the correlation between the expression of TASK-1 mRNA on the low brainstem and the sleep apnea index of Sprague-Dawley rats was analyzed. Study on the relationship between TASK-1 and sleep apnea
【学位授予单位】：河北医科大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R363

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