Boutros Cherif, Zegdi Rachid, Lila Nermine, Cambillau Michele, Fornes Paul, Carpentier Alain, Fabini Jean Noel
Laboratory of the Study of Cardiac Grafts and Protheses, Broussias Hospital, Paris, France.
J Surg Res. 2007 Dec;143(2):437-42. doi: 10.1016/j.jss.2007.02.013. Epub 2007 Sep 7.
Pulmonary expression of heme oxygenase has been observed in multiple studies. This expression has been found beneficial in decreasing the severity of acute lung injury (ALI) post ischemia-reperfusion (I/R). The aim of this study was to assess the role of exogenous administration of the end-products of heme oxygenase reaction, carbon monoxide, and bilirubin, in the severity of ALI.
We compared five groups of rats (n = 7/group) including a sham group and four I/R of the lower extremities by clamping the abdominal aorta for 2 h followed by reperfusion for 2 h. The four I/R groups included a control group, one pretreated with bilirubin (50 micromol/kg IV), another with inhaled carbon monoxide (CO) (250 ppm), and the last pretreated with both. The severity of ALI has been evaluated by a histological assay grading neutrophilic infiltration, as well as a study of the microvascular permeability using the Evans blue.
The administration of CO prevented pulmonary microvascular permeability alteration noted after I/R of the lower limbs (pulmonary content of Evans blue: 141 +/- 23 microg/g of tissue in the isolated I/R group versus 68 +/- 34 microg/g of tissue in CO group; P < 0.001). Histologically CO administration inhibited neutrophilic sequestration observed after I/R. On the other hand, treatment by bilirubin alone (50 micromol/kg IV) did not modify the extent of pulmonary injury.
Exogenous administration of carbon monoxide by inhalation at low doses prevented ALI post-I/R in this model.
多项研究观察到血红素加氧酶在肺部的表达。已发现这种表达有助于降低缺血再灌注（I/R）后急性肺损伤（ALI）的严重程度。本研究的目的是评估血红素加氧酶反应终产物一氧化碳和胆红素的外源性给药在ALI严重程度中的作用。
我们比较了五组大鼠（每组n = 7），包括假手术组和四组下肢I/R组，通过夹闭腹主动脉2小时，随后再灌注2小时。四组I/R组包括对照组、一组用胆红素预处理（静脉注射50微摩尔/千克）、另一组吸入一氧化碳（CO）（250 ppm），最后一组同时用两者预处理。通过组织学分析对中性粒细胞浸润进行分级来评估ALI的严重程度，并使用伊文思蓝研究微血管通透性。
给予CO可防止下肢I/R后出现的肺微血管通透性改变（伊文思蓝肺组织含量：单纯I/R组为141±23微克/克组织，CO组为68±34微克/克组织；P < 0.001）。组织学上，给予CO可抑制I/R后观察到的中性粒细胞滞留。另一方面，单独用胆红素治疗（静脉注射50微摩尔/千克）并未改变肺损伤的程度。
在该模型中，低剂量吸入外源性一氧化碳可预防I/R后的ALI。
