Protection Of N-acetylcysteine In Rat Lung From Ischemia-reperfusion Injury

Pulmonary injury after ischemia and reperfusion, which occurs in many clinical conditions such as lung transplantation, cardiopulmonary bypass(CPB), and pulmonary embolism, is a major cause of pulmonary dysfunction following the clinical conditions. Pulmonary ischemia-reperfusion (I/R) injury is a complicated pathologic process caused by multiple factors. Nuclear factor-κB (NF-κB) is an important transcription factor in cell signaling system. And it plays a key role in pulmonary I/R injury. We regard NF-κB as the target, and reduce the activation of NF-κB with the inhibitor: N-acetylcysteine (NAC). Consequently we can attenuate the pulmonary I/R injury.Objective: Single lung in situ ischemia-reperfusion animal model was used to investigate the protective effects of NAC on pulmonary ischemia-reperfusion injury and its possible mechanism.Methods: Thirty male Wistar rats (weight of 260~290g) were randomly divided into three groups (n=10): Control group (sham I/R group); I/R group (simple I/R group); NAC group (NAC treated group). Single lung in situ ischemia-reperfusion animal model was established with occlusion of pulmonary hilus in I/R group and NAC group. The left lungs of rats were rendered normothermic ischemia for 45 minutes and reperfusion for 3 hours. There was no treatment of I/R in control group. The NAC group were injected NAC (200mg·kg-1) intraperitoneally 30 minutes before ischemia. All animals were killed at the end of reperfusion. The lung tissue wet-to-dry (W/D) ratio, activity of myeloperoxidase (MPO) and content of malondialdehyde (MDA) were measured. The pathological changes were observed by the H-E staining of the tissular sections. The protein expression of NF-κBp65 and intercellular adhesion molecule-1 (ICAM-1) were also detected by immunohistochemical staining and image analysis.Results: (1) There were remarkable pathological manifestations of pulmonary injury in I/R group. Compared with the I/R group, the pathomorphology changes of NAC group were ameliorated. (2) In I/R group, the W/D ratio,content of MDA and activity of MPO in lung tissue after reperfusion were significantly higher than those of control group (P< 0.01). Compared with I/R group, the levels of W/D ratio, MDA and MPO were decreased in NAC group (P< 0.01). (3) Compared with control group, the expression of NF-κBp65 and ICAM-1 were up-regulated significantly in I/R group (P< 0.01). The levels of NF-κBp65 and ICAM-1 were decreased...