Effects of anesthesia-related substance orexin on respiratory neurons in the isolated brainstem-spinal cord preparation of newborn rats

挥发性麻醉剂对呼吸活动的抑制作用是通过其对中枢呼吸控制的作用引起的。以往的研究表明，挥发性麻醉剂通过对GABA受体的作用来诱导麻醉作用。然而，内源性神经肽食欲素最近被认为在麻醉的睡眠/觉醒中起重要作用。因此，本项目利用新生大鼠的脑干-脊髓制剂分析了食欲素对中枢呼吸控制的影响。食欲素B的应用导致C4经脑干而非脊髓破裂率呈剂量依赖性增加。C4爆发率的增加引起吸气前（Pre-I）神经元和吸气前（Insp）神经元去极化周期率的增加。C4和Pre-I神经元的节律性爆发最终变为强直性爆发，而Insp神经元的节律性爆发则保持不变。本研究结果表明，Orexin B主要通过i前神经元和inp神经元的去极化和膜阻力的增加来激活中枢呼吸活动，并可能通过Exp神经元的去极化诱导呼气期提前开始。

Inhibitory effects of volatile anesthetic on respiratory activities are induced through its effects on central respiratory control. Past papers indicates that volatile anesthetic are though to induce aneshetic effects by its effects on GABA receptor. However, endogeneous neuropeptide orexin is recently believed to play an important role in sleep/wakefukness of anesthesia. Thus, this project analyse effects of orexin on central respiratory control using brainstem-spinal cord preparation of newborn rats. The application of Orexin B resulted in dose-dependent increases in C4 burst rate via brainstem, not via spinal cord. The increases in C4 burst rate induced concomitant increases in the depolarizing cycle rate of preinspiratory (Pre-I) neurons and inspiratory (Insp) neurons. The rhythmic bursts of C4 and Pre-I neurons finally became to be tonic, although the rhythmic bursts of Insp neurons were maintained. Expiratory (Exp) neurons were also depolarized by the application of Orexin B. Our findings indicate that Orexin B activates central respiratory activity mainly through depolarizing and increases in membrane resistance of Pre-I neurons and Insp neurons, and possibly through early start of expiratry phase induced by depolarization of Exp neurons.