Role of nitric oxide and peroxynitrite anion in lung injury induced by intestinal ischemia-reperfusion in rats

摘要

AIM: To evaluate effects of nitric oxide (NO) and peroxynitrite anion (ONOO-) on lung injury following intestinal ischemia-reperfusion (IR) in rats. METHODS: A rat model of intestinal ischemia was made by clamping superior mesenteric artery and lung injury was resulted from reperfusion. The animals were randomly divided into 3 groups: sham operation (Sham), 2 h ischemia followed by 2 h reperfusion (IR) and IR pretreated with aminoguanidine (AG) - an inhibitor of inducible NO synthase (iNOS) 15 minutes before reperfusion (IR+AG). The lung malondialdehyde (MDA) and nitrate/nitrite (NO2/NO3)contents and morphological changes were examined.Western blot was used to detect the iNOS protein expression.Immunohistochemical staining was used to determine the change of nitrotyrosine (NT)- a specific 'footprint' of ONOO-. RESULTS: The morphology revealed evidence for lung edema, hemorrhage and polymorphonuclear sequestration after intestinal IR. Compared with sham group, lung contents of MDA and NO2-/NO3- in IR group were significantly increased (12.00±2.18 vs23.44±1.25 and 76.39±6.08 vs140.40±4.34,P＜0.01) and the positive signals of iNOS and NT were also increased in the lung. Compared with IR group, the contents of MDA and NO2/NO3 in IR+AG group were significantly decreased (23.44±1.25 vs14.66±1.66 and 140.40±4.34 vs 80.00±8.56, P＜0.01) and NT staining was also decreased. CONCLUSION: Intestinal IR increases NO and ONOO production in the lung, which may be involved in intestinal IR-mediated lung injury.