异丙酚的意识消失作用与睡眠-觉醒系统的相关性研究

The mechanism study of consciousness lose during general anesthesia is the main direction in the research field of anesthesia. Consciousness lose during general anesthesia were similar to sleep, there is a connection between anesthesia and central sleep-awake system, however, the effects of general anesthetics on the sleep system is poorly understood. VLPO is a critical nucleus of induction and maintenance of sleep，VLPO sleep system is the ideal object for the study of relationship between sleep and general anesthesia..Based on previous work about loss of consciousness , we use the methods of whole cell patch clamp to investigate the effects of propofol on the electrical excitation and key ion channels of VLPO neurons. We believe that this project can elucidate the mechanisms of anesthetics effects on hypnotic system.

明确全麻意识消失的机制是全身麻醉药物作用研究的重要内容。全身麻醉导致的意识消失与自然睡眠之间存在高度的相似性，全麻意识消失的过程很有可能涉及睡眠通路的激活，但还未有研究能够阐明两者间的具体关系。VLPO是诱导和维持睡眠的关键核团，以其为核心的睡眠系统是研究全麻机制和睡眠机制相关性的理想对象。本项目基于前期研究全麻意识消失的工作基础，利用脑片膜片钳技术观察全麻药物异丙酚对VLPO神经元电兴奋性和关键离子通道的影响，旨在从中枢睡眠发生角度解释全麻意识消失的机制。

本课题组在专项基金项目的资助下，借助大鼠脑片膜片钳技术，观察了全麻药物异丙酚对大鼠睡眠中枢——下丘脑腹外侧视前核(The ventrolateral preoptic nucleus, VLPO)内神经元的神经元膜电位、动作电位发放、抑制性突触后电流、兴奋性突触后电流和钠钾离子通道电流的影响，在离子通道水平研究异丙酚对 VLPO 神经元的作用。.完成情况概述：.1.成功建立了VLPO核团内不同类别神经元的鉴别方法，即区分NA(+)神经元和NA(-)神经元。NA(-)神经元是VLPO核团内主要的功能性神经元，是本项目的实验对象。.2.记录并对比了异丙酚作用前后VLPO神经元动作电位发放的变化。.3.记录了异丙酚作用前后VLPO神经元抑制性突触后电流和兴奋性突触后电流的改变。.4.记录了不同浓度异丙酚作用下VLPO神经元钠钾离子通道电流的变化。.5.观察了阻断VLPO神经元上胆碱能受体、多巴胺能受体和组胺能受体对异丙酚作用下VLPO神经元抑制性突触后电流的影响。.通过对大鼠睡眠相关VLPO核的神经元不同受体和离子通道的研究，明确了静脉麻醉药异丙酚对VLPO神经元电活动的影响，为借助睡眠探究全身麻醉作用机制相关的研究奠定了一定的实验基础。