Simpson V J, Blednov Y
Department of Anesthesiology, University of Colorado Health Sciences Center, Denver, USA.
Anesth Analg. 1996 Feb;82(2):327-31. doi: 10.1097/00000539-199602000-00020.
We report differential central nervous system (CNS) sensitivity to propofol between Long Sleep (LS) and Short Sleep (SS) mice, selectively bred for their differential CNS sensitivity to ethanol. Intravenous propofol requirements for loss of righting reflex, or sleep time, were measured to define the extent of this sensitivity. LS mice slept approximately two times longer than SS mice at equal doses. Awakening plasma and brain levels of the SS line were, respectively, two and three times that of the LS line (P < 0.0001). This suggests that the LS and SS sleep time difference is CNS mediated, and that propofol and ethanol may share common genes that determine anesthetic sensitivities. The ethanol effect may be at least partially mediated by gamma-aminobutyric acid-A (GABAA) receptor function. Propofol had no differential effect on GABAA receptor function, as measured by chloride flux in LS and SS brain microsac preparations. Either the GABAA receptor does not mediate propofol sleep time, or qualitative differences cannot be demonstrated using 36Cl- uptake in brain membranes.
我们报告了长睡眠（LS）小鼠和短睡眠（SS）小鼠对丙泊酚的中枢神经系统（CNS）敏感性差异，这两种小鼠是因其对乙醇的中枢神经系统敏感性差异而选择性培育的。通过测量翻正反射消失或睡眠时间的静脉注射丙泊酚需求量来确定这种敏感性的程度。在同等剂量下，LS小鼠的睡眠时间比SS小鼠长约两倍。SS品系苏醒时的血浆和脑内丙泊酚水平分别是LS品系的两倍和三倍（P < 0.0001）。这表明LS和SS小鼠睡眠时间的差异是由中枢神经系统介导的，并且丙泊酚和乙醇可能共享决定麻醉敏感性的共同基因。乙醇的作用可能至少部分由γ-氨基丁酸-A（GABAA）受体功能介导。通过测量LS和SS脑微粒体制剂中的氯离子通量发现，丙泊酚对GABAA受体功能没有差异影响。要么GABAA受体不介导丙泊酚睡眠时间，要么使用脑膜中的36Cl摄取无法证明其质量差异。
