Résumé
Abstract Purpose: To investigate the effect of dexmedetomidine (Dex) in a rat ex vivo lung model of ischemia-reperfusion injury. Methods: An IL-2 ex vivo lung perfusion system was used to establish a rat ex vivo lung model of ischemia-reperfusion injury. Drugs were added to the perfusion solution for reperfusion. Lung injury was assessed by histopathological changes, airway pressure (Res), lung compliance (Compl), perfusion flow (Flow), pulmonary venous oxygen partial pressure (PaO2), and lung wet/dry (W/D) weight ratio. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), 78 kDa glucose-regulated protein (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) were measured, respectively. Results: The introduction of Dex attenuated the post-ischemia-reperfusion lung damage and MDA level, improved lung histology, W/D ratio, lung injury scores and SOD activity. Decreased mRNA and protein levels of GRP78 and CHOP compared with the IR group were observed after Dex treatment. The effect of Dex was dosage-dependence and a high dose of Dex (10 nM) was shown to confer the strongest protective effect against lung damage (P<0.05). Yohimbine, an α2 receptor antagonist, significantly reversed the protective effect of Dex in lung tissues (P<0.05). Conclusion: Dex reduced ischemia-reperfusion injury in rat ex vivo lungs.
Sujets)
Animaux , Mâle , Lésion d'ischémie-reperfusion/prévention et contrôle , Dexmédétomidine/pharmacologie , Agonistes des récepteurs alpha-2 adrénergiques/pharmacologie , Ischémie/prévention et contrôle , Poumon/vascularisation , Valeurs de référence , Superoxide dismutase/analyse , Facteurs temps , Lésion d'ischémie-reperfusion/anatomopathologie , Technique de Western , Reproductibilité des résultats , Résultat thérapeutique , Rat Sprague-Dawley , Protéines liant les séquences stimulatrices de type CCAAT/analyse , Modèles animaux de maladie humaine , Réaction de polymérisation en chaine en temps réel , Protéines du choc thermique/analyse , Poumon/anatomopathologie , Malonaldéhyde/analyseRésumé
ABSTRACT Introduction Recently, expression of the UHRF1 gene was found to be up-regulated in numerous neoplasms, including the urinary bladder transitional cell carcinoma (TCC). Objective The aim of our study was to determine if the expression levels of UHRF1 gene correlates with the major pathological characteristics of the tumor and patients’ clinical outcome. Materials and Methods In our study, we have analyzed the tissue samples derived from group of 70 patients with histologically confirmed TCC of the urinary bladder, while normal urinary bladder mucosa obtained from 40 patients with nonmalignant diseases was used as a negative control group. Expression of UHRF1 gene in each patient sample was determined using reverse transcriptase-polymerase chain reaction. Results UHRF1 gene expression was found to be app. 2.5 times higher in samples from patients with TCC in comparison with normal epithelium derived from control group patients. Analysis show that gene expression correlates with the malignancy of the tumor. A highly significant differences were found between the expression values of samples from low and high grade TCC, as well as between the high grade and control group. UHRF1 expression was higher in patients with non-muscle invasive disease than in those with muscle invasive disease. Conclusions The result of this study indicates that UHRF1 gene expression levels correlates with the major pathological characteristics of TCC samples and with the clinical outcome of those patients. Determination of UHRF1 gene expression could have a potential to be used as a sensitive molecular marker in patients with urinary bladder cancer.