Park Hee-Pyoung, Jeon Young-tae, Hwang Jung-won, Kang Hoon, Lim Seung-Woon, Kim Chong-Sung, Oh Yong-Seok
Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Seongnam 463-707, Republic of Korea.
Neurosci Lett. 2005 Oct 21;387(2):90-4. doi: 10.1016/j.neulet.2005.06.072.
We examined in a rabbit model of transient spinal cord ischemia (SCI) whether isoflurane (Iso) preconditioning induces ischemic tolerance to SCI in a dose-response manner, and whether this effect is dependent on mitochondrial adenosine triphosphate-dependent potassium (K(ATP)) channel. Eighty-six rabbits were randomly assigned to 10 groups: Control group (n=8) received no pretreatment. Ischemic preconditioning (IPC) group (n=8) received 5 min of IPC 30 min before SCI. The Iso 1, Iso 2 and Iso 3 groups (n=10, 9, 8) underwent 30 min of 1.05, 2.1 and 3.15% Iso inhalation commencing 45 min before SCI. The Iso 1HD, Iso 2HD and Iso 3HD groups (n=9, 9, 8) each received a specific mitochondrial K(ATP) channel blocker, 5-hydroxydecanoic acid (5HD, 20mg/kg), 5 min before each respective Iso inhalation. The 5HD group (n=8) received 5HD without Iso inhalation. The sham group (n=9) had no SCI. SCI was produced by infra-renal aortic occlusion via the inflated balloon of a Swan-Ganz catheter for 20 min. The Iso 1, Iso 2 and Iso 3 groups showed a better neurologic outcome and more viable motor nerve cells (VMNCs) in the anterior spinal cord 72 h after reperfusion than the control group (p<0.05). Iso 3 group showed a better neurologic outcome and more VMNCs than Iso 1 group (p<0.05). And, the Iso 1, Iso 2 and Iso 3 groups showed a better neurologic outcome and higher VMNC numbers than the corresponding Iso 1HD, Iso 2HD and Iso 3HD groups (p<0.05). This study demonstrates that Iso preconditioning protects the spinal cord against neuronal damage due to SCI in a dose-response manner via the activation of mitochondrial K(ATP) channels.
我们在兔短暂性脊髓缺血（SCI）模型中研究了异氟烷（Iso）预处理是否以剂量反应方式诱导对SCI的缺血耐受性，以及这种效应是否依赖于线粒体三磷酸腺苷依赖性钾（K(ATP)）通道。86只兔被随机分为10组：对照组（n = 8）未接受预处理。缺血预处理（IPC）组（n = 8）在SCI前30分钟接受5分钟的IPC。Iso 1组、Iso 2组和Iso 3组（n = 10、9、8）在SCI前45分钟开始进行30分钟的1.05%、2.1%和3.15%异氟烷吸入。Iso 1HD组、Iso 2HD组和Iso 3HD组（n = 9、9、8）在各自异氟烷吸入前5分钟分别接受特异性线粒体K(ATP)通道阻滞剂5-羟基癸酸（5HD，20mg/kg）。5HD组（n = 8）接受5HD但未吸入异氟烷。假手术组（n = 9）未进行SCI。通过Swan-Ganz导管的充气气囊进行肾下主动脉闭塞20分钟以产生SCI。再灌注72小时后，Iso 1组、Iso 2组和Iso 3组在前脊髓中的神经功能结局更好，存活的运动神经细胞（VMNCs）更多，优于对照组（p<0.05）。Iso 3组的神经功能结局和VMNCs数量优于Iso 1组（p<0.05）。并且，Iso 1组、Iso 2组和Iso 3组的神经功能结局更好，VMNCs数量更多，优于相应的Iso 1HD组、Iso 2HD组和Iso 3HD组（p<0.05）。本研究表明，Iso预处理通过激活线粒体K(ATP)通道以剂量反应方式保护脊髓免受SCI所致的神经元损伤。
