Effects Of Ulinastain Pretreatment On The Expresstion Of MtTFA In Lung Tissue During The Lung Injury By Induced One-lung Ventilation In Rabbits

Objective：Long time during one lung ventilation induced lung injury,patients was induced complications of severe pulmonary edema and expiratorydyspnea[1]. To explore the pathological mechanism is significant for itsprevention and treatment[2].Research shows that injury of lungs can damagethe mitochondrial DNA (mtDNA), lead to mitochondrial dysfunction[3].Mitochondrial transcription factor A (mtTFA) is an important promoter ofmitochondrial DNA replication.The study show overexpression of mtTFAprotein can stabilize the levels of mtDNA in muscle cells, mtTFA is importantin maintaining mtDNA stability[4]. Mitochondrial transcription factor A(mtTFA) is an important promoter of mitochondrial DNA transcription andtranslation of mitochondrial structure and function of protein protein.Researchshows that relieves oxidative stress during the lung injury by induced one lungventilation[5].This study was to evaluate one lung ventilation induced changesin expression of mitochondrial transcription factor A in lung tissue injury inrabbit lung, and the influence of ulinastatin intervention, in order to clarify themechanism of single lung ventilation induced lung injury and lung protectionof ulinastatin, provides the reference for the clinical research.Methods: Twenty-four healthy male rabbits weight2.5-3.0kg wererandomized into3groups (n=8each): double-lung ventilation group (groupD); one-lung ventilation group (group O); Ulinastain group (group U). Therabbit model of One-lung ventilation intubates endotracheal which usedself-made double lumen. Group D double lung ventilation3h,2h afterbeginning One-lung ventilation and1h after returning to double-lungventilation in group O, group U successful immediate intravenous Ulinastatin50kU/kg, subsequently2h after beginning One-lung ventilation in left lung and1h after returning to doule-lung ventilation. Animal was routine fastingfor12h，and no water for8h.3%pentobarbital30mg/kg intravenousanesthesia, the right femoral artery and femoral vein catheterization, arteryintubation for invasive arterial pressure monitoring, venous catheter forinfusion and blood sampling.T group and O group of intravenous saline.Ventilation parameters for24ml VTof doule-lung ventilation, VTof one-lungventilation were12ml, FiO2100%, RR40bpm, I:E=1:2. Immediately beganVentilation (T0),1h of ventilation(T1),2h of ventilation (T2), ventilation over(T3)，collection of arterial blood oxygenation index of arterial were taken forblood gas analysis. After the thoracotomy for bilateral ventilation apexorganization, using chemical colorimetric detection of lung tissue MDAassaying and SOD activity were observed by HE staining; histopathologicalfindings, lung tissue injury score, expression of mtTFA was determined byimmunohistochemical and western blot in lung tissue of rabbit.Results:1. The changes of Oxygenation index on arterial blood in rabbits.Oxygenation index was significantly decreased in group O compare withgroup D（P<0.05）2. Bilateral lung of alveolar was intact basically in group D by lightmicroscopic, no obvious exudation, no hemorrhage,no interstitial thickening,and no inflammatory cell infiltrated; the left lung of alveolar structure wasdisappear in group O, obvious exudation, alveolar hemorrhage, interstitialthickening, many inflammatory cells; the right lung of alveolar structure wasdestroyed, obvious exudation, alveolar hemorrhage, interstitial thickening,many inflammatory cells were decreased in group O. Degree of injury wasdecreased significantly in group U of bilateral compare with group O.3. Lung injury score,SOD activity, MDA assaying, the expression ofmtTFA were on difference significantly in left lung of group D compare withright of group D（P>0.05）；Lung injury score was increased significantly,SOD activity was decreased significantly, MDA assaying was increasedsignificantly, the expression of mtTFA was decreased significantly in the rightlung of group O compare with the left lung of group O（P<0.05）.Lung injury score was increased significantly, SOD activity was decreased significantly,MDA assaying was increased significantly, the expression of mtTFA wasdecreased significantly in the left lung of group O compare with the left lungof group D（P<0.05）.4.Lung injury score was increased significantly, SOD activity wasdecreased significantly, MDA assaying was increased significantly, theexpression of mtTFA was decreased significantly in group O and group Ucompare with group D（P<0.05）.Lung injury score was decreased significantly,SOD activity was increased significantly, MDA assaying was decreasedsignificantly, the expression of mtTFA was increased significantly in the leftlung of group U compare with the left lung of group O（P<0.05）..Lung injuryscore was decreased significantly, SOD activity was increased significantly,MDA assaying was decreased significantly, the expression of mtTFA wasincreased significantly in the right lung of group U compare with the rightlung of group O（P<0.05）.Conclusions:1. Long time one-lung ventilation could provoke acutelung injury, which was inhomogeneous.The degrees of lung injury wererelated to one-lung ventilation duration and were more severe in thenon-ventilated lung. ulinastatin has protective effect on the. Ulinastainpretreatment probably play an important role in lung injury caused byone-lung ventilation.2. The primary cause of the lung injury induced by one-lung ventilation islipid peroxidation in lung tissue.its mechanism may be down-regulation ofmtTFA expression in the lung tissue.3.Ulinastatin pretreatment relieves oxidative stress during the lung injuryinduced by one-lung ventilation, its mechanism probably play an importantrole up-regulation expression of mtTFA in the lung tissue.