Nitrite reduces ischemia/reperfusion-induced muscle damage and improves survival rates in rat crush injury model
Nitrite reduces ischemia/reperfusion-induced muscle damage and improves survival rates in rat crush injury model
复制标题
DOI：
10.1097/ta.0b013e31824a76b5
复制
发表时间：
2012-06-01
影响因子：
3.4
通讯作者：
Kobayashi, Jun
中科院分区：
文献类型：
--
作者：
Murata, Isamu;Nozaki, Ryo;Kobayashi, Jun
背景：亚硝酸盐是一种内在信号分子，在哺乳动物心脏、肝脏和肾脏缺血再灌注（I/R）损伤中具有潜在的治疗意义。虽然肢体肌肉压迫和随后的再灌注是发生挤压综合征（CS）的原因，但尚未有报道评价亚硝酸盐对CS的治疗效果。因此，我们测试了亚硝酸盐是否可以作为治疗CS的治疗剂。方法：采用麻醉大鼠双侧后肢橡胶止血带压迫5 h，再灌注0 ~ 6 h，同时监测血压，建立CS模型。再灌注前立即静脉给予CS组生理盐水或亚硝酸钠（NaNO2-100、200和500 mu mol/kg）。采集血液和组织样本进行生化分析。结果：在I/R损伤期间，与假手术组相比，CS组损伤肌肉组织亚硝酸盐水平明显降低。给CS大鼠施用亚硝酸盐，通过提高肌肉中的亚硝酸盐水平，从而恢复一氧化氮的生物利用度，从而减少横纹肌溶解标志物，如钾、乳酸脱氢酶和肌酸磷酸激酶。亚硝酸盐治疗还降低了血浆白细胞介素-6水平和肌肉和肺组织中的髓过氧化物酶活性，最终导致存活率的剂量依赖性改善，从24% （CS组）提高到36% （NaNO2-100组）和64% （NaNO2-200组和500组）。结论：上述结果表明，亚硝酸盐通过其细胞保护作用减轻I/ r诱导的肌肉损伤，有助于提高大鼠CS模型的存活率。[J]创伤急症护理杂志，2012;72:1548-1554。版权所有：Lippincott Williams & Wilkins)。
BACKGROUND: Nitrite is an intrinsic signaling molecule with potential therapeutic implications in mammalian ischemia/reperfusion (I/R) injury of the heart, liver, and kidney. Although limb muscle compression and subsequent reperfusion are the causative factors in developing crush syndrome (CS), there has been no report evaluating the therapeutic effects of nitrite on CS. We therefore tested whether nitrite could be a therapeutic agent for the treatment of CS.METHODS: To create a CS model, anesthetized rats were subjected to bilateral hind limb compression with rubber tourniquets for 5 hours, followed by reperfusion for 0 hour to 6 hours while monitoring blood pressure. Saline for the CS group or sodium nitrite (NaNO2-100, 200, and 500 mu mol/kg) for the nitrite-treated CS groups was intravenously administered immediately before reperfusion. Blood and tissue samples were collected for biochemical analysis.RESULTS: Tissue nitrite levels in injured muscles were significantly reduced in the CS group compared with the sham group during I/R injury. Nitrite administration to CS rats restored nitric oxide bioavailability by enhancing nitrite levels of the muscle, resulting in a reduction of rhabdomyolysis markers such as potassium, lactate dehydrogenase, and creatine phosphokinase. Nitrite treatment also reduced plasma levels of interleukin-6 and myeloperoxidase activities in muscle and lung tissues, finally resulting in a dose-dependent improvement of survival rate from 24% (CS group) to 36% (NaNO2-100 group) and 64% (NaNO2-200 and 500 groups).CONCLUSION: These results indicate that nitrite reduces I/R-induced muscle damage through its cytoprotective action and contributes to improved survival rate in a rat CS model. (J Trauma Acute Care Surg. 2012;72: 1548-1554. Copyright (C) 2012 by Lippincott Williams & Wilkins).