The Influence Of Ulinastatin On The Lung Injury Induced By Hyperoxia Mechanical Ventilation In Pigs

Objective: Oxygen is necessary to the activity of life. Appropriateoxygen therapy has certain effects on health care and treatment. However,prolonged high concentration of oxygen administered to patients may causeoxidation-antioxidant system imbalance with lung epithelia cell. The lung asthe first direct contact with the organs was most likely to be caused oxidativelung injury. Ulinastatin (UTI) which is purified from the healthy adult malefresh urine is a kind of typical Kuniz protease inhibitors. Besides the strongenzyme inhibition, Ulinastatin can inhibit the release of inflammation factors,improve the decreased immune function by surgical stimulation, attenuates thedamage of organ and tissue coming from the surgical stimulation. It showsstrong viscera protection function, reducing oxygen free radicals. In this study,the establishment of the hyperoxia-induced lung injury model of pigs is usedto monitor the amount of serum neutrophil elastase (NE) and electronmicroscopy. Observing and analyzing the protective effect of ulinaststin onhyperoxia lung injury in order to provide effective experimental basis forulinastain in the clinical practice.Methods:Twelve pigs were randomly divided into two groups: hyperoxiamechanical ventilation group (group H, fractional inspired oxygenconcentration was100％, n=6) and UTI treated group (W group, factionalinspired oxygen concentration was100％,n=6). Induction of anesthesia withintramuscular ketamine (20mg/kg) and atropine (0.05mg/kg) was conductedroutinely in order to open vein pass. Endotracheal intubation was employed bylaryngoscope and Datex–Ohmeda anaesthetic apparatus was used tomechanical ventilation. The pig's heart rate,mean arterial pressure and PETCO2were measured. Anesthetic gas monitor (PHILIPS MP50) was used toexamine breathy frequency and peaks of respiratory organs. The amount ofneutrophil elastase(NE)in lung tissue was measured by enzyme linkedimmunosorbent assay(ELISA) at basic level0,5and7h respectively duringgeneral anesthesia. At the same time, two or three pulmonary tissues were cutfrom low lobe of the right lung.The lung structure of two groups wasobserved with transmission electron microscopy and microscope.Results:1. The general data of the two groups' pig isn't different. There was nosignificantly different between the two groups at the HR,PETCO2, PpeakandMAP(P>0.05).2．Compared with the basic level, The quantity of NE in Group H wereincreased significantly at7h (P<0.01); There were distinction of NE betweengroup H and W(P<0.01).3the pathologic change of the lung tissue under the optical microscopeCompared with group W, the pathologic change of the lung tissue wasobviously aggravated at the hyperoxia mechanical ventilation group. There areobvious of focus hemorrhage, inflammatory cell infiltration and thickeningalveolar septum. The change of the lung tissues of UTI treated group waslightener than hyperoxia mechanical ventilation group at different times.4Ultrastructural changes of the lung tissue with electronic microscopeThere was significantly difference between group H and W. At7h ofhyperoxia mechanical ventilation,the damage, swelling and exfoliation ofAEC-Ⅰ were observed. The loosen lamellar bodies in AEC-Ⅱ and swollenpartial pulmonary capillary endothelial cells were seen. The continuitybetween endothelial cells and basement membrane was damaged. The normalstructure of AEC-II and pulmonary capillary endothelial cell weredisappeared.there were more neutrophil infiltration and the swelling ofalveolar interstitial.Conclusion: Long time (7hours)inhalation of high concentrations of oxygen cancause a certain degree of lung injury. UTI may have certain protective effecton hyperoixa-induced lung injury.