The Protective Effects Of NDRG2on Pulmonary Tissue Of Rat With Acute Lung Injury Induced By Intestinal Ischemia-reperfusion Injury

Background：Despite refinements in lung preservation and improvements in the in surgicaltechniques and perioperative care, acute lung injury(ALI) remains a significant cause ofearly morbidity and mortality while recanalization after intravenous thrombolysis or organtransplantation. Intestinal ischemia/reperfusion (II/R) is a potentially serious consequenceof several clinical and pathophysiological conditions including small boweltransplantation, cardiopulmonary bypass, trauma, and hemorrhage[1–4].Reperfusion of thegut after an ischemic episode is associated with a progressive loss of the mucosal structurewith denuded and shrunken villi and a reduced epithelial function, thus eventually leadingto a loss of barrier integrity and translocation of luminal antigens and bacteria[1,5,6]. II/R isan important event in the pathogenesis of multiple organ dysfunction syndrome (MODS), especially the acute respiratory distress syndrome (ARDS)[2,3]. However, the precisemechanisms of II/R induced lung injury remain unclear.The nuclear factor kappa B (NF-κB) proteins are a family of transcriptional factorscontrolling the expression of many genes in immune and acute-phase inflammatoryresponses, cell adhesion, differentiation, oxidative stress responses, and apoptosis[7,8].Nuclear factor kappa B plays a major role during the local and systemic inflammatoryresponse following II/R[9,10]. In addition, modulating the NF-κB pathway is a new conceptand therapeutic strategy to attenuate the lung injury caused by II/R[11,12].N-myc downstream regulated gene2（NDRG2）belongs to the NDRG family whichcomprises four members: NDRG1-4. Previous studies have shown that NDRG2is highlyexpressed in human lung tissue[13]. NDRG2overexpression reduces phospho-IKKα/βexpression following suppression of subsequent IκBα degradation and p65nucleartranslocation[14]. The NDRG family is highly conserved among many species such as hearttissue and leydig cell which is indicative of the importance of its biological functions[15,16].ObjectiveTo explore the expression of N-myc downstream regulated gene2（NDRG2）andnuclear factor κB in intestinal ischemia/reperfusion induced lung injury. To discuss therole of NF-κB signal transduction pathway in the pathological changes of acute lunginjury. These might be the potential targets in the treatment of II/RI.Methods：1. The level of NDRG2and NF-κB expression in intestinal ischemia/reperfusioninduced lung injury were detected by immunohistochemisty and Western Blot.2. The level of NDRG2and NF-κB mRNA expression in intestinalischemia/reperfusion induced lung injury were detected by RT-PCR3. To analyze the correlation between NDRG2and NF-κB.4. TUNEL was used to detect the apoptosis of cells.Results：1. Immunohistochemisty and Western Blot showed that the expression of NF-κB weresignificantly upregulated while NDRG2were downregulated in intestinal ischemia/reperfusion induced lung injury（P<0.05）, the result was statistically significant．2. RT-PCR showed that the level of NF-κB mRNA expression rised and NDRG2decreased in experimental group（P<0.05）, the result was statistically significant．3. NDRG2and NF-κB was negatively correlated（r=-0.814, P<0.05）, the result wasstatistically significant．4. Compared with the control group ((1.21±0.71)%)，the percentage of apoptotic cellsincreased significantly after ischemia-reperfusion. I/R group, in turn, respectively（16.21±1.34）%,（37.91±2.15）%,（24.15±2.43）%,（17.15±2.53）%, P<0.05, the result wasstatistically significant．Conclusions：The NDRG2expression in the lung tissue was downregulated and activated, whichgives a hint that NF-κB signal transduction could play an important role in thepathogenesis of pathological changes in intestinal ischemia/reperfusion induced lunginjury.