Involvement of nitric oxide system in experimental muscle crush injury
Involvement of nitric oxide system in experimental muscle crush injury
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DOI：
10.1172/jci810
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发表时间：
1998-03-15
影响因子：
15.9
通讯作者：
Better, OS
中科院分区：
文献类型：
--
作者：
Rubinstein, I;Abassi, Z;Better, OS
肌肉挤压伤常并发血流动力学休克、电解质紊乱和肌红蛋白尿性肾功能衰竭。在这项研究中，我们研究了一氧化氮（NO）系统的参与在肌肉损伤的发展中的实验模型的挤压伤引起的施加标准化的机械压力对大鼠胫骨肌。完整的肢体作为对照。损伤后4天，挤压肌肉的特征在于极端毛细血管扩张，如组织形态学分析所示。这些变化伴随着通过测量股动脉血流（超声血流仪）和毛细血管血流（激光多普勒血流仪）评估的肌肉过度灌注。用一氧化氮合酶（NOS）抑制剂N ω-硝基-L-精氨酸甲酯治疗，大大降低了过度灌注。此外，不同的NOS亚型的表达，通过逆转录-PCR和免疫反应水平，通过Western印迹法测定评估，揭示了一个显着的诱导型NOS在破碎的肢体诱导。同样，内皮型一氧化氮合酶mRNA在诱导肌肉损伤后逐渐增加。相反，主要肌肉NOS，即，神经元亚型保持不变。与mRNA水平的改变一致，Western印迹分析显示各种NOS的免疫反应水平的平行变化。这些结果表明，肌肉挤压与激活的NO系统，主要是由于增强NOS。这可能有助于NO依赖性的过度血管扩张，并加重挤压伤后的低血容量性休克。
Muscle crush injury is often complicated by hemodynamic shock, electrolyte disorders, and myoglobinuric renal failure. In this study, we examined the involvement of the nitric oxide (NO) system in the development of muscle damage in an experimental model of crush injury induced by exertion of standardized mechanical pressure on tibialis muscle of rat. The intact limb served as a control. Four days after injury, the crushed muscle was characterized by extreme capillary vasodilatation as demonstrated by histological morphometric analysis. These changes were accompanied by muscle hyperperfusion as evaluated by measurements of femoral blood flow (ultrasonic flowmetry) and capillary blood flow (laser-doppler flowmetry). Treatment with N omega-nitro-L-arginine methyl ester, a NO synthase (NOS) inhibitor, largely decreased the hyperperfusion. Furthermore, the expression of the different NOS isoforms, assessed by reverse transcription-PCR and immunoreactive levels, determined by Western blot, revealed a remarkable induction of the inducible NOS in the crushed limb. Similarly, endothelial NOS mRNA increased gradually after the induction of muscle damage. In contrast, the major muscular NOS, i.e., neuronal isoform remained unchanged. In line with the alterations in the mRNA levels, Western blot analysis revealed parallel changes in the immunoreactive levels of the various NOS. These findings indicate that muscle crush is associated with activation of the NO system mainly due to enhancement of NOS. This may contribute to NO-dependent extreme vasodilatation in the injured muscle and aggravate the hypovolemic shock after crush injury.