Deree Jessica, Martins Joilson O, Leedom Alex, Lamon Brian, Putnam James, de Campos Tercio, Hoyt David B, Wolf Paul, Coimbra Raul
Division of Trauma and Surgical Critical Care, Department of Surgery, University of California School of Medicine, San Diego, CA, USA.
J Trauma. 2007 Jan;62(1):104-11. doi: 10.1097/TA.0b013e31802d96cb.
Ringer's lactate (RL), the current standard resuscitation fluid, potentiates neutrophil activation and is associated with pulmonary inflammation. Resuscitation with hypertonic saline and pentoxifylline (HSPTX) has been shown to attenuate hemorrhagic shock-induced injury when compared with RL. Because the neutrophil plays a major role in postshock inflammation, we hypothesized that HSPTX reduces pulmonary inflammation after resuscitation in comparison to RL.
Sprague-Dawley rats underwent controlled shock and were resuscitated with RL (32 mL/kg) or HSPTX (4 mL/kg 7.5% NaCl + pentoxifylline 25 mg/kg). Animals who did not undergo shock or resuscitation served as controls. After 24 hours, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. Cytokine induced neutrophil chemoattractant (CINC) was measured in BALF by enzyme-linked immunosorbent assay. Matrix metalloproteinases (MMP)-2 and -9 were measured by zymography. Hemeoxygenase-1 (HO-1) was assessed by Western blot and immunohistochemistry.
HSPTX resuscitation led to a 62% decrease in CINC levels compared with RL (p < 0.01). BALF MMP-2 expression was attenuated by 11% with HSPTX (p = 0.09). Lung MMP-2 and MMP-9 expression was reduced by 89% (p < 0.01) and 76%, respectively (p < 0.05). Lung HO-1 expression declined by 34% with HSPTX in comparison to RL (p < 0.01), indicating less oxidative injury. Lung immunohistochemistry localized HO-1 to neutrophils, macrophages, and airway epithelial cells.
Collectively, the attenuation of pulmonary inflammation with HSPTX after shock when compared with RL is associated with downregulation of neutrophil activation, oxidative stress, and proinflammatory mediator production.
乳酸林格氏液（RL）是目前标准的复苏液体，可增强中性粒细胞活化并与肺部炎症相关。与RL相比，高渗盐水和己酮可可碱（HSPTX）复苏已显示可减轻失血性休克引起的损伤。由于中性粒细胞在休克后炎症中起主要作用，我们假设与RL相比，HSPTX可减轻复苏后的肺部炎症。
将Sprague-Dawley大鼠进行控制性休克，并用RL（32 mL/kg）或HSPTX（4 mL/kg 7.5%氯化钠+己酮可可碱25 mg/kg）进行复苏。未经历休克或复苏的动物作为对照。24小时后，收集支气管肺泡灌洗液（BALF）和肺组织。通过酶联免疫吸附测定法测量BALF中的细胞因子诱导的中性粒细胞趋化因子（CINC）。通过酶谱法测量基质金属蛋白酶（MMP）-2和-9。通过蛋白质印迹和免疫组织化学评估血红素加氧酶-1（HO-1）。
与RL相比，HSPTX复苏导致CINC水平降低62%（p < 0.01）。HSPTX使BALF中MMP-2表达降低11%（p = 0.09）。肺MMP-2和MMP-9表达分别降低89%（p < 0.01）和76%（p < 0.05）。与RL相比，HSPTX使肺HO-1表达下降34%（p < 0.01），表明氧化损伤较小。肺免疫组织化学将HO-1定位于中性粒细胞、巨噬细胞和气道上皮细胞。
总体而言，与RL相比，休克后HSPTX减轻肺部炎症与中性粒细胞活化、氧化应激和促炎介质产生的下调有关。
