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吸入一氧化氮对盐水灌洗兔急性肺损伤模型氧化应激及肺组织病理和炎症损伤的影响。

Effects of inhaled nitric oxide on oxidative stress and histopathological and inflammatory lung injury in a saline-lavaged rabbit model of acute lung injury.

机构信息

Departamento de Pediatria Botucatu, Sao Paulo State University, Sao Paulo, Brazil.

出版信息

Respir Care. 2012 Feb;57(2):273-81. doi: 10.4187/respcare.01289. Epub 2011 Jul 12.

DOI:10.4187/respcare.01289
PMID:21762562
Abstract

BACKGROUND

Conventional mechanical ventilation (CMV) is fundamental in acute respiratory distress syndrome (ARDS) treatment. Inhaled nitric oxide (INO), an adjunctive therapy, has been used with ventilation in an attempt to improve oxygenation and reduce lung injury.

OBJECTIVE

To analyze the early effects of low INO dose on oxygenation, oxidative stress, inflammatory, and histopathological lung injury in a rabbit model of acute lung injury (ALI).

METHODS

This was a prospective, controlled, in vivo animal laboratory study. Forty rabbits were instrumented and ventilated at F(IO(2)) 1.0. ALI was induced by tracheal infusion of warm saline (30 mL/kg, 38°C) and lung oxidative stress was assessed by total antioxidant performance (TAP) assay. Animals were assigned to groups: control group (no. = 10, low tidal volume [V(T)] = 6 mL/kg, PEEP = 5 cm H(2)O), ALI without INO (no-INO group, no. = 10, low V(T) = 6 mL/kg, PEEP = 10 cm H(2)O), ALI plus INO (INO group, no. = 10, low V(T) = 6 mL/kg, PEEP = 10 cm H(2)O, INO = 5 ppm). Plateau pressure was limited to 30 cm H(2)O in all groups. Ten non-instrumented animals (healthy group) were studied for TAP assay. Ventilatory and hemodynamic parameters were recorded every 30 min for 4 hours.

RESULTS

After lung injury, the instrumented groups were worse than the control group for P(aO(2)) (control group 438 ± 87 mm Hg, no-INO group 80 ± 13 mm Hg, INO group 81 ± 24 mm Hg, P < .001). The INO group showed decreased lung inflammation by leukocyte count in lung lavage fluid (no-INO group 4.8 ± 1.64, control group 0.16 ± 0.15, INO group 0.96 ± 0.35 polymorphonuclear cells × 10(6)/bronchoalveolar lavage fluid/lung, P < .001), decreased histopathological injury score (no-INO group 5 [range 1-16], INO group 2 [range 0-5], control group 0 [range 0-3], P < .001), and better lung protection against oxidative injury than the no-INO group (healthy group 68 ± 8.7, control group 66.4 ± 6.8, INO group 56.3 ± 5.1, no-INO group 45.9 ± 3.4 percent protection/g protein, P < .001).

CONCLUSIONS

INO attenuates oxidative stress and histopathological and inflammatory lung injury in a saline-lavaged rabbit ALI model.

摘要

背景

传统机械通气(CMV)是急性呼吸窘迫综合征(ARDS)治疗的基础。吸入一氧化氮(INO)作为一种辅助治疗方法,已与通气联合应用,试图改善氧合并减轻肺损伤。

目的

分析INO 低剂量对兔急性肺损伤(ALI)模型中氧合、氧化应激、炎症和组织病理学肺损伤的早期影响。

方法

这是一项前瞻性、对照、体内动物实验室研究。40 只兔子接受仪器检测并进行 F(IO(2))1.0 的通气。通过气管内输注温盐水(30 mL/kg,38°C)诱导 ALI,并通过总抗氧化能力(TAP)测定评估肺氧化应激。动物被分为以下几组:对照组(n = 10,低潮气量 [V(T)] = 6 mL/kg,PEEP = 5 cm H(2)O)、无 INO 的 ALI 组(no-INO 组,n = 10,低 V(T)= 6 mL/kg,PEEP = 10 cm H(2)O)、INO 加 ALI 组(INO 组,n = 10,低 V(T)= 6 mL/kg,PEEP = 10 cm H(2)O,INO = 5 ppm)。所有组的平台压均限制在 30 cm H(2)O。10 只未仪器检测的动物(健康组)用于 TAP 测定。每 30 分钟记录一次通气和血流动力学参数,共 4 小时。

结果

肺损伤后,与对照组相比,仪器检测组的 PaO(2)更差(对照组 438 ± 87 mmHg,无 INO 组 80 ± 13 mmHg,INO 组 81 ± 24 mmHg,P <.001)。INO 组通过肺灌洗液中白细胞计数降低了肺炎症(无 INO 组 4.8 ± 1.64,对照组 0.16 ± 0.15,INO 组 0.96 ± 0.35 个中性粒细胞×10(6)/支气管肺泡灌洗液/肺,P <.001),降低了组织病理学损伤评分(无 INO 组 5 [范围 1-16],INO 组 2 [范围 0-5],对照组 0 [范围 0-3],P <.001),并比无 INO 组更好地保护肺免受氧化损伤(健康组 68 ± 8.7,对照组 66.4 ± 6.8,INO 组 56.3 ± 5.1,无 INO 组 45.9 ± 3.4%保护/g 蛋白,P <.001)。

结论

INO 减轻了盐水灌洗兔 ALI 模型中的氧化应激以及组织病理学和炎症性肺损伤。

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