کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4303563 | 1288482 | 2009 | 13 صفحه PDF | دانلود رایگان |
BackgroundPrevious investigations have shown that short term inhalation of nitric oxide (NO) before ischemia and reperfusion (I/R) prevents I/R-related consequences on lung function. Here we correlate effects of NO-induced preconditioning, especially on the lung permeability barrier, with analysis of cell junction proteins and the level of vascular endothelial growth factor (VEGF).MethodsA rat model of left lung in situ I/R was used. After left lateral thoracotomy, left lung ischemia was maintained for 60 min, followed by 30 min or 4 h (h) reperfusion (I/R groups). In the NO groups, inhalation of NO (10 min, 15 ppm) preceded I/R. Animals in control groups underwent sham surgery without NO inhalation and ischemia. The extent of I/R injury was assessed in terms of oxygenation (arterial PO2) and lung permeability (Evans blue extravasation). Expression of junctional proteins and phosphorylation was determined in complete protein extracts from lung tissue, whereas the adherens junction (AJ) core complex was analyzed in Triton extracts by co-immunoprecipitation using antibodies against E-cadherin and VE-cadherin.ResultsThe inhalation of NO prevented the I/R-induced increase of permeability at 30 min reperfusion, and the PO2 increased from 27% of controls in the I/R group to 77% in the NO group. Left lung I/R correlated with a progressive loss of cadherins (VE-cadherin, E-cadherin, desmoglein 1) during reperfusion, whereas AJ catenins were largely preserved. Preconditioning with NO resulted in an increased ratio of catenins (α- and β-catenin) to E-cadherin in immunoprecipitates and in reduced phosphorylation of β-catenin. A reduction of VEGF in left lung lavage fluid was observed at 4 h but not at 30 min reperfusion.ConclusionsThe NO-induced changes of the AJ complex may have contributed to the stabilization of the lung permeability barrier during reperfusion.
Journal: Journal of Surgical Research - Volume 157, Issue 1, November 2009, Pages 30–42