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

吸入麻醉药对呼吸活动的抑制作用是通过影响中枢呼吸控制而产生的。以往的研究表明，挥发性麻醉药是通过影响GABA受体而产生麻醉作用的。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，本课题采用新生大鼠脑干-脊髓标本研究食欲素对中枢呼吸控制的影响。Orexin B的应用导致通过脑干而不是通过脊髓的C4爆发率的剂量依赖性增加。C4爆发率的增加引起吸气前（Pre-I）神经元和吸气（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紧张性的，尽管Insp神经元的节律性爆发得以维持。应用Orexin B也使呼气（Exp）神经元去极化。我们的研究结果表明，Orexin B激活中枢呼吸活动，主要通过去极化和增加前I神经元和Insp神经元的膜电阻，并可能通过早期开始呼气相诱导的Exp神经元的去极化。

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.