Extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) pathways involved in spinal cord stimulation (SCS)-induced vasodilation.
Extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) pathways involved in spinal cord stimulation (SCS)-induced vasodilation.
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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。
DOI：
10.1016/j.brainres.2007.12.072
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发表时间：
2008
期刊：
影响因子：
2.9
通讯作者：
Foreman,RobertD
中科院分区：
文献类型：
--
作者：
Wu,Mingyuan;Komori,Naoka;Qin,Chao;Farber,JayP;Linderoth,Bengt;Foreman,RobertD
背景和AIMSSCS用于改善肢体缺血患者的外周循环。然而，这些机制还没有完全被理解。本研究探讨阻断ERK和AKT激活是否对SCS诱导的血管扩张有调节作用。方法在大鼠腰椎2~3节段左侧背柱放置单极球电极。用激光多普勒血流监测仪记录左、右后足垫的皮肤血流量。SCS通过球状电极在MT的60%或90%处施加。ERK的抑制剂U0126或PI3K的抑制剂LY294002分别作用于腰椎3~5个节段(每组7个)。结果SU0126(100nM、5μM和250nM)在60%(分别为100nM：P<；0.05；5μM和250nM：P<；0.01)和90%的MT(分别为100nM和5μM：P<；0.01)可显著减弱脊髓的血管扩张作用。LY294002在100μ时，可分别在MT的60%和90%时减弱脊髓刺激的血管扩张作用(P<；0.05)。
BACKGROUND AND AIMSSCS 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.METHODSA 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).RESULTSU0126 (100 nM, 5 μM and 250 μM) significantly attenuated SCS-induced vasodilation at 60% (100 nM: P<0.05; 5 μM and 250 μM: P<0.01, respectively) and 90% of MT (100 nM and 5 μM: P<0.05; 250 μM: P<0.01, respectively). LY294002 at 100 μM also attenuated SCS-induced vasodilation at 60% and 90% of MT (P<0.05).CONCLUSIONSThese data suggest that ERK and AKT pathways are involved in SCS-induced vasodilation.