化学性急性呼吸窘迫综合征时一氧化碳、血红素加氧酶及一氧化氮的变化

目的　探讨一氧化碳 (CO)及血红素加氧酶 (HO)在化学性急性呼吸窘迫综合征(ARDS)肺循环障碍发生机制中的作用 ,并与一氧化氮 (NO)的作用相比较。方法　制备油酸型ARDS大鼠模型后 ,测定不同病程肺动脉、颈动脉、颈静脉血及支气管肺泡灌洗液 (BALF)中CO和NO的含量 ,同时采用免疫组化法检测HO在肺组织内的表达情况。结果　给大鼠注射油酸后 10min ,肺动脉压力增高 (从 13 80mmHg增加到 19 5 1mmHg) ;0 5h时肺动脉血中CO水平开始升高 ,2h后显著高于对照组 [(0 135± 0 0 10 )g/L ,(0 116± 0 0 0 5 )g/L]及同时间点颈动脉血和静脉血 (0 117± 0 0 13)g/L ,(0 10 7± 0 0 18)g/L ;0 5～ 2 4h ,BALF中CO浓度明显升高 ;ARDS大鼠肺动脉血和外周动、静脉血中NO水平均较对照组明显升高 ,12h后降至正常水平 ,各时间点BALF中NO浓度均显著高于对照组 ;ARDS各组大鼠动脉血PaO2 均显著低于对照组。免疫组化显示正常大鼠肺内组织可见HO 2表达 ,以支气管上皮细胞表达最强 ;而HO 1只在大鼠注射油酸后的肺血管壁、支气管上皮细胞、肺泡上皮细胞和炎症细胞内表达 ,并持续 72h ,与CO水平增高情况相一致。结论　油酸性ARDS大鼠肺循环血中CO水平持续升高 ,提示CO/HO系统在ARDS发病中可能比一氧化氮及其合酶系统具有更

Changes of carbon monoxide, nitric oxide levels and heme oxygenase system in acute respiratory distress syndrome induced by oleic acid

OBJECTIVE: To investigate possible role of carbon monoxide (CO) and heme oxygenase (HO) in the pathogenesis of acute respiratory distress syndrome (ARDS) induced by oleic acid (OA) and to compared with that induced by nitric oxide (NO). METHODS: ARDS model was established in rats by oleic acid injection and concentrations of CO and NO in pulmonary arterial, carotid jugular blood and bronchoalveolar lavage fluid (BALF) were measured sequentially. Immunohistochemical method was used to determine the expression of HO in the lung. RESULTS: Pulmonary arterial pressure in ARDS rats elevated 10 min after OA injection [(13.80 +/- 1.87) mm Hg to (19.51 +/- 5.02) mm Hg]. At 0.5 h after OA injection, concentration of CO in pulmonary artery began to increase and was markedly higher at 2 h than that in control rats [(0.135 +/- 0.010) g/L versus (0.116 +/- 0.005) g/L] (P < 0.01), also higher than that in carotid artery [(0.117 +/- 0.013) g/L] and in jugular vein [(0.107 +/- 0.018) g/L] in the same group, and maintained at a relatively high level thereafter. Concentration of CO in BALF also increased at 0.5 - 24 h and diminished at 72 h, as compared with that in controls. Concentration of NO in blood of pulmonary and systemic circulation all elevated markedly at 0.5 h and 2 h after OA injection, and then declined to normal at 12 h. Concentration of NO in BALF was significantly higher than that in controls. Arterial blood gas analysis showed that PaO2 markedly decreased in ARDS rats, especially at 2 h after OA injection. HO-2 could be expressed in the lung tissues of normal rats with immunohistochemical method, the strongest in epithelial cells of the bronchi, and HO-1 could only be expressed in pulmonary blood vessel walls, bronchial epithelial cells, alveolar epithelial cells and inflammatory cells of ARDS rats, lasting for 72 h after OA injection, consistent with that of CO level. CONCLUSION: ARDS rats showed a lastecl increase of CO level in pulmonary blood circulation, suggesting CO/HO system might play a more important role in modulation of blood vessel tension than NO might do in pathogenesis of ARDS.