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Three-dimensional analysis and molecular Mechanism of the autonomic nervous system in chronically hypoxic carotid body

颈动脉体慢性缺氧自主神经系统三维分析及分子机制

基本信息

批准号：
11670015
负责人：
KUSAKABE Tatsumi
金额：
$ 2.24万
依托单位：
Kokushikan University (2000)Yokohama City University (1999)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

The carotid bodies, which are the primary sensory organs for sensing changes in arterial blood gases and hydrogen ion concentration, were enlarged in the rat exposed to chronic hypo-, iso-, and hypercapnic hypoxia. In the hypo- and isocapnic hypoxia, the density of VIP fibers increased significantly, and the density of NPY fibers were unchanged. In the hypercapnic hypoxia, the density of NPY fibers was significantly increased, and that of VIP was unchanged. Because these neuropeptides are vasoactive in nature, altered carotid body circulation may contribute to modulation of the chemosensory mechanisms by chronic hypoxia. Three-dimensional analysis showed that these peptidergic fibers are mainly associated with expanded vasculatures. In addition, calbindin D-28k fibers in the hypoxic carotid bodies was significantly decreased. The carotid body one month after the termination of chronic hypoxia was diminished in size, and the density of NPY fibers was increased.The hypoxia induced either an increase or a decrease in [Ca^<2+>] i in glomus cells. ACh and NaCN mostly increased in [Ca^<2+>] i in glomus cells, and maintained 50% of the amplitude of this [Ca^<2+>] response under the removal of Ca^<2+>. On the basis of these results, we proposed a model of intracellular and cell-to-fiber chemo-transduction in response to chemical stimuli. Relatively large number of glomus cells represent hyperpolarization, while a small number of cells represent depolarization. Gap junction and reciprocal synapses are depicted as important structures for interaction among glomus cells and afferent terminals. Some afferent nerve fibers produced no discharge, since the glomus cells apposed by their terminals do not depolarize, but rather hyperpolarize. A further study is necessary to elucidate what triggers chemo-transduction mechanism.

颈动脉小体是感知动脉血气和氢离子浓度变化的主要感觉器官，暴露于慢性低、等、高碳酸缺氧的大鼠颈动脉小体增大。在低氧和等氧条件下，VIP纤维密度显著增加，NPY纤维密度不变。在高碳酸缺氧时，NPY纤维密度显著增加，VIP纤维密度不变。由于这些神经肽在本质上具有血管活性，颈动脉循环的改变可能有助于慢性缺氧对化学感觉机制的调节。三维分析表明，这些肽能纤维主要与血管扩张有关。此外，低氧颈动脉小体中的calbindin D-28k纤维明显减少。慢性缺氧结束1个月后颈动脉体缩小，NPY纤维密度增加。缺氧诱导血管球细胞[Ca^<2+>] i升高或降低。ACh和NaCN主要在球囊细胞[Ca^<2+>] i中增加，在去除Ca^<2+>后，仍维持该[Ca^<2+>]反应幅度的50%。在这些结果的基础上，我们提出了一个响应化学刺激的细胞内和细胞到纤维的化学转导模型。较多的球囊细胞呈超极化，少部分细胞呈去极化。间隙连接和互反突触被描述为球囊细胞和传入终端之间相互作用的重要结构。一些传入神经纤维不产生放电，因为其末端的血管球细胞不去极化，而是超极化。需要进一步的研究来阐明是什么触发了化学转导机制。