Department of Anesthesiology, Children's Hospital of Chongqing Medical University, PR China.
Brain Res Bull. 2011 Aug 10;86(1-2):29-35. doi: 10.1016/j.brainresbull.2011.06.017. Epub 2011 Jul 2.
Propofol is currently one of the most widely used intravenous anesthetic. In the present study, we investigated the effects of propofol on neuropathogenesis in newborn rats under hypoxic conditions. Seven-day old SD rats were assigned into one of the six treatments: propofol+50% oxygen (propofol-oxygen, PO), propofol+room air (propofol-air, PA), propofol+18% oxygen (propofol-hypoxia, PH), control group: lipid emulsion solvent+50% oxygen (CO), lipid emulsion solvent+room air (CA), lipid emulsion solvent+18% oxygen (CH). The rats assigned to anesthesia or control groups received intraperitoneally (ip) propofol 50 mg/kg or identical volume of lipid emulsion solvent (5.0 ml/kg) for seven days. SaO(2) (%) and respiratory rate (RR) were monitored throughout the procedures. The rats were decapitated 24h after 7 days exposure. TUNEL staining, Nissl staining, ultrastructural changes and the expression of caspase-3 in the brain tissues were assessed. We found propofol-induced attenuation of respiration could produce lower oxygen concentrations in the blood (hypoxia) under air or mild hypoxia conditions. Interestingly, in the presence of oxygen completely rescued hypoxia to normal levels, suggesting that propofol-induced respiratory depression led to hypoxia only under air or mild hypoxic conditions (propofol/hypoxia). In addition, propofol indirectly induced apoptosis through hypoxia resulting from respiratory depression under air or hypoxic conditions, which was determined by elevated expression of caspase-3, increased TUNEL-positive cells, ultrastructural changes of neuronal cell death and loss of Nissl staining neuronal in infant SD rat brains. However, in propofol-oxygen group and all control groups, no significant apoptosis were observed. These findings indicated that propofol per se or hypoxia per se did not directly induce significant apoptosis. However, propofol-induced attenuation of respiration could produce lower oxygen concentrations in the blood under air or mild hypoxia conditions and thereby result in neuronal degeneration. So, it is important to supply with supplementary oxygen during propofol anesthesia.
丙泊酚目前是最广泛使用的静脉麻醉剂之一。在本研究中，我们研究了丙泊酚在新生大鼠缺氧条件下对神经发病机制的影响。将 7 日龄 SD 大鼠分为以下 6 种处理组之一：丙泊酚+50%氧气（丙泊酚-氧气，PO）、丙泊酚+室内空气（丙泊酚-空气，PA）、丙泊酚+18%氧气（丙泊酚-缺氧，PH）、对照组：脂质乳剂溶剂+50%氧气（CO）、脂质乳剂溶剂+室内空气（CA）、脂质乳剂溶剂+18%氧气（CH）。接受麻醉或对照组的大鼠接受腹膜内（ip）丙泊酚 50mg/kg 或相同体积的脂质乳剂溶剂（5.0ml/kg）7 天。整个过程中监测 SaO2（%）和呼吸频率（RR）。7 天暴露后 24 小时处死大鼠。评估脑组织中的 TUNEL 染色、尼氏染色、超微结构变化和 caspase-3 的表达。我们发现，丙泊酚诱导的呼吸抑制在空气或轻度低氧条件下会导致血液中氧气浓度降低（缺氧）。有趣的是，在氧气存在的情况下，完全将缺氧恢复到正常水平，表明丙泊酚诱导的呼吸抑制仅在空气或轻度低氧条件下导致缺氧（丙泊酚/缺氧）。此外，丙泊酚通过在空气或低氧条件下呼吸抑制引起的缺氧间接诱导细胞凋亡，这通过 caspase-3 表达升高、TUNEL 阳性细胞增加、神经元细胞死亡的超微结构变化和尼氏染色神经元丧失来确定。然而，在丙泊酚-氧气组和所有对照组中，没有观察到明显的细胞凋亡。这些发现表明，丙泊酚本身或缺氧本身不会直接引起明显的细胞凋亡。然而，丙泊酚诱导的呼吸抑制会导致血液中的氧气浓度降低，在空气或轻度低氧条件下导致神经元变性。因此，在丙泊酚麻醉期间，补充氧气非常重要。
