Fang Bo, Li Xiao-Qian, Bi Bo, Tan Wen-Fei, Liu Gang, Zhang Ying, Ma Hong
Department of Anesthesiology, First Affiliated Hospital, China Medical University, Liaoning, P. R. China.
Cell Physiol Biochem. 2015;36(1):373-83. doi: 10.1159/000430107. Epub 2015 May 6.
BACKGROUND/AIMS: Dexmedetomidine has beneficial effects on ischemia reperfusion (I/R) injury to the spinal cord, but the underlying mechanisms are not fully understood. This study investigated the effects and possible mechanisms of dexmedetomidine on blood-spinal cord barrier (BSCB) disruption induced by spinal cord I/R injury.
Rats were intrathecally pretreated with dexmedetomidine or PBS control 30 minutes before undergoing 14-minute occlusion of aortic arch. Hind-limb motor function was assessed using Tarlov criteria, and motor neurons in the ventral gray matter were counted by histological examination. The permeability of the BSCB was examined using Evans blue (EB) as a vascular tracer. The spinal cord edema was evaluated using the wet-dry method. The expression and localization of matrix metalloproteinase-9 (MMP-9), Angiopoietin-1 (Ang1) and Tie2 were assessed by western blot, real-time polymerase chain reaction, and immunofluorescence.
Intrathecal preconditioning with dexmedetomidine minimized the neuromotor dysfunction and histopathological deficits, and attenuated EB extravasation after spinal cord I/R injury. In addition, dexmedetomidine preconditioning suppressed I/R-induced increase in MMP-9. Finally, Dexmedetomidine preconditioning enhanced the Ang1-Tie2 system activity after spinal cord I/R injury.
Dexmedetomidine preconditioning stabilized the BSCB integrity against spinal cord I/R injury by inhibition of MMP-9, and enhancing the Ang1-Tie2 system.
背景/目的：右美托咪定对脊髓缺血再灌注（I/R）损伤具有有益作用，但其潜在机制尚未完全明确。本研究探讨右美托咪定对脊髓I/R损伤所致血脊髓屏障（BSCB）破坏的影响及可能机制。
大鼠在主动脉弓阻断14分钟前鞘内注射右美托咪定或PBS作为对照进行预处理。采用Tarlov标准评估后肢运动功能，通过组织学检查计数腹侧灰质中的运动神经元。使用伊文思蓝（EB）作为血管示踪剂检测BSCB的通透性。采用干湿法评估脊髓水肿情况。通过蛋白质印迹法、实时聚合酶链反应和免疫荧光法评估基质金属蛋白酶-9（MMP-9）、血管生成素-1（Ang1）和Tie2的表达及定位。
右美托咪定鞘内预处理可使脊髓I/R损伤后的神经运动功能障碍和组织病理学损伤降至最低，并减轻EB外渗。此外，右美托咪定预处理可抑制I/R诱导的MMP-9增加。最后，右美托咪定预处理可增强脊髓I/R损伤后Ang1-Tie2系统的活性。
右美托咪定预处理通过抑制MMP-9和增强Ang1-Tie2系统来稳定BSCB完整性，以抵抗脊髓I/R损伤。
