First Affiliated Hospital of Nanjing Medicial University, Jiangsu, China.
Chin Med J (Engl). 2010 Apr 20;123(8):1039-46.
Treatment with inhaled carbon monoxide (CO) has been shown to ameliorate intestinal injury in experimental animals induced by lipopolysaccharide (LPS) or ischemia-reperfusion. We hypothesized that CO intraperitoneal administration (i.p.) might provide similar protection to inhaled gas. This study aimed to investigate the effects of continuous 2 L/min of 250 ppm CO i.p. on rat intestine injury induced by LPS and to try to develop a more practical means of delivering the gas.
A total of 72 male Sprague-Dawley rats were randomly assigned to 4 groups: control group, CO i.p. group, LPS group and LPS+CO i.p. group. One hour after intravenously received 5 mg/kg LPS, the rats in LPS group and LPS+CO i.p. group were exposed to room air and 2 L/min of 250 ppm CO i.p., respectively, and the rats of control group and CO i.p. group intravenously received an equal volume of 0.9% NaCl and 1 hour later, were exposed to room air and 2 L/min of 250 ppm CO i.p., respectively. One, 3 and 6 hour of each group after treated with room air or CO i.p., the animals (n = 6 for each time point) were sacrificed and intestinal tissues were collected for determinating the levels of platelet activator factor (PAF) and intercellular adhesion molecule-1 (ICAM-1) with enzyme-lined immunosorbent assays. The maleic dialdehyde (MDA) content and the myeloperoxidase (MPO) activity were determined with a chemical method. The phosphorylated p38 mitogen activated protein kinase (MAPK) expression was assayed with Western blotting and the cell apoptotic rate with flow cytometery. The arterial oxygenation was measured by blood gas analysis, and the pathology determined by light microscope.
After treatment with 2 L/min of 250 ppm CO i.p., the increase of PAF, ICAM-1, MDA, MPO, and cell apoptotic rate induced by LPS was markedly reduced (P < 0.05 or 0.01), and accompanied by ameliorating intestine injury. Western blotting showed that these effects of CO i.p. were mediated by p38 MAPK pathway. There were no significant differences in all observed parameters between control group and CO i.p. group.
The injury to the intestine via anti-oxidant, anti-inflammation and anti-apoptosis, which may involve the p38 MAPK pathway, was induced by 2 L/min of 250 ppm CO i.p. exerting potent protection against LPS.
吸入一氧化碳（CO）已被证明可改善实验动物中由脂多糖（LPS）或缺血再灌注引起的肠损伤。我们假设腹腔内给予 CO（i.p.）可能会提供类似的保护作用。本研究旨在探讨持续 2 L/min 250 ppm CO i.p. 对 LPS 诱导的大鼠肠损伤的影响，并尝试开发更实用的输送气体方法。
72 只雄性 Sprague-Dawley 大鼠随机分为 4 组：对照组、CO i.p. 组、LPS 组和 LPS+CO i.p. 组。静脉注射 5mg/kg LPS 1 小时后，LPS 组和 LPS+CO i.p. 组大鼠分别暴露于室内空气和 2 L/min 250 ppm CO i.p.，对照组和 CO i.p. 组大鼠分别静脉注射等容量的 0.9% NaCl，1 小时后分别暴露于室内空气和 2 L/min 250 ppm CO i.p.。每组大鼠在暴露于室内空气或 CO i.p. 后 1、3 和 6 小时（每个时间点 6 只动物）处死并收集肠组织，用酶联免疫吸附试验测定血小板激活因子（PAF）和细胞间黏附分子-1（ICAM-1）的水平。用化学方法测定丙二醛（MDA）含量和髓过氧化物酶（MPO）活性。用 Western 印迹法测定磷酸化 p38 丝裂原激活蛋白激酶（p38 MAPK）的表达，用流式细胞术测定细胞凋亡率。用血气分析测定动脉氧合，用光学显微镜测定病理学。
腹腔内给予 2 L/min 250 ppm CO i.p. 后，LPS 诱导的 PAF、ICAM-1、MDA、MPO 和细胞凋亡率的增加明显减少（P<0.05 或 0.01），并伴有肠损伤的改善。Western 印迹显示，CO i.p. 的这些作用是通过 p38 MAPK 途径介导的。对照组和 CO i.p. 组之间所有观察参数均无显著差异。
2 L/min 250 ppm CO i.p. 通过抗氧化、抗炎和抗凋亡作用诱导肠损伤，可能涉及 p38 MAPK 途径，对 LPS 具有强大的保护作用。
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