细胞外信号调节激酶（ERK）和蛋白激酶B（AKT）通路参与脊髓刺激（SCS）诱导的血管舒张。
Extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) pathways involved in spinal cord stimulation (SCS)-induced vasodilation.
作者信息
Wu Mingyuan, Komori Naoka, Qin Chao, Farber Jay P, Linderoth Bengt, Foreman Robert D
机构信息
Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190, USA.
出版信息
Brain Res. 2008 May 1;1207:73-83. doi: 10.1016/j.brainres.2007.12.072. Epub 2008 Jan 12.
BACKGROUND AND AIMS
SCS is used to improve peripheral circulation in selected patients with ischemia of the extremities. However the mechanisms are not fully understood. The present study investigated whether blockade of ERK and AKT activation modulated SCS-induced vasodilation.
METHODS
A unipolar ball electrode was placed on the left dorsal column at the lumbar 2-3 spinal segments in rats. Cutaneous blood flows from left and right hind foot pads were recorded with laser Doppler flow perfusion monitors. SCS was applied through a ball electrode at 60% or 90% of MT. U0126, an inhibitor of ERK kinase, or LY294002, an inhibitor of PI3K upstream of AKT, was applied to the lumbar 3-5 spinal segments (n=7, each group).
RESULTS
U0126 (100 nM, 5 microM and 250 microM) significantly attenuated SCS-induced vasodilation at 60% (100 nM: P<0.05; 5 microM and 250 microM: P<0.01, respectively) and 90% of MT (100 nM and 5 microM: P<0.05; 250 microM: P<0.01, respectively). LY294002 at 100 microM also attenuated SCS-induced vasodilation at 60% and 90% of MT (P<0.05).
CONCLUSIONS
These data suggest that ERK and AKT pathways are involved in SCS-induced vasodilation.
背景与目的
脊髓刺激（SCS）用于改善特定肢体缺血患者的外周循环。然而，其机制尚未完全明确。本研究探讨了阻断细胞外信号调节激酶（ERK）和蛋白激酶B（AKT）激活是否会调节SCS诱导的血管舒张。
方法
将单极球形电极置于大鼠腰2 - 3脊髓节段的左侧背柱上。用激光多普勒血流灌注监测仪记录左右后足垫的皮肤血流。通过球形电极以阈强度（MT）的60%或90%施加SCS。将ERK激酶抑制剂U0126或AKT上游的磷脂酰肌醇-3激酶（PI3K）抑制剂LY294002应用于腰3 - 5脊髓节段（每组n = 7）。
结果
U0126（100 nM、5 μM和250 μM）在MT的60%（100 nM：P < 0.05；5 μM和250 μM：分别为P < 0.01）和90%时显著减弱SCS诱导的血管舒张（100 nM和5 μM：P < 0.05；250 μM：P < 0.01）。100 μM的LY294002在MT的60%和90%时也减弱SCS诱导的血管舒张（P < 0.05）。
结论
这些数据表明ERK和AKT信号通路参与SCS诱导的血管舒张。
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