Savas S, Savas C, Altuntas I, Adiloglu A
Department of Physical Medicine and Rehabilitation, Süleyman Demirel University Medical School, Isparta, Turkey.
Spinal Cord. 2008 Feb;46(2):113-7. doi: 10.1038/sj.sc.3102066. Epub 2007 Apr 10.
Prospective, randomized, placebo-controlled, experimental study.
The issue of whether nitric oxide (NO) production is beneficial or deleterious on ischemic injuries of the central nervous system still remains doubtful. Vascular endothelial growth factor (VEGF) is known to induce the release of NO from endothelial cells. However, the effect of NO on VEGF synthesis is not clear. We aimed to determine the effects of L-arginine and NG-nitro-L-arginine methyl ester (L-NAME) on VEGF synthesis and free radicals in a rat model of spinal cord ischemia-reperfusion (IR) injury.
Surgical Research Laboratory of a Medical School.
Twenty-eight Wistar rats were divided into four groups as follows (n=7): Sham, IR injury, L-arginine, and L-NAME. Infrarenal abdominal aorta was occluded to induce spinal cord ischemia. L-Arginine (100 mg/kg) and L-NAME (10 mg/kg) were given before aortic occlusion. Biochemical assays of malondialdehyde (MDA), NO and VEGF were carried out in spinal cord specimens.
L-Arginine treatment significantly increased MDA and NO, but decreased VEGF levels in spinal cord. However, nonselective inhibition of NOS with L-NAME significantly decreased MDA and NO, but increased VEGF levels. Besides, the positive linear correlation between MDA and NO, and negative linear correlations between MDA, NO and VEGF levels have also been demonstrated.
Nonselective inhibition of NO synthase activity with L-NAME attenuated free radical formation and increased VEGF level when compared with NO precursor L-arginine in a rat model of spinal cord ischemia. We suggest that inhibition of NO synthase, as well as induction of VEGF, may be a therapeutic option in spinal cord IR injury.
前瞻性、随机、安慰剂对照实验研究。
一氧化氮（NO）生成对中枢神经系统缺血性损伤是有益还是有害这一问题仍存疑问。已知血管内皮生长因子（VEGF）可诱导内皮细胞释放NO。然而，NO对VEGF合成的影响尚不清楚。我们旨在确定L-精氨酸和NG-硝基-L-精氨酸甲酯（L-NAME）对脊髓缺血再灌注（IR）损伤大鼠模型中VEGF合成和自由基的影响。
一所医学院的外科研究实验室。
28只Wistar大鼠分为以下四组（n = 7）：假手术组、IR损伤组、L-精氨酸组和L-NAME组。阻断肾下腹主动脉以诱导脊髓缺血。在主动脉阻断前给予L-精氨酸（100 mg/kg）和L-NAME（10 mg/kg）。对脊髓标本进行丙二醛（MDA）、NO和VEGF的生化检测。
L-精氨酸治疗显著增加了脊髓中的MDA和NO，但降低了VEGF水平。然而，L-NAME对一氧化氮合酶的非选择性抑制显著降低了MDA和NO，但增加了VEGF水平。此外，还证实了MDA与NO之间呈正线性相关，MDA、NO与VEGF水平之间呈负线性相关。
在脊髓缺血大鼠模型中，与NO前体L-精氨酸相比，L-NAME对一氧化氮合酶活性的非选择性抑制减弱了自由基形成并增加了VEGF水平。我们认为，抑制一氧化氮合酶以及诱导VEGF可能是脊髓IR损伤的一种治疗选择。
