Experimental Study On The Therapeutic Effect Of Ulinastatin Against Acute Lung Injury Caused By Paraquat Poisoning

BackgroundParaquat(1,1'-dimethyl-4,4'-bipyridylium) was originally developed in English in 1995 as a bipyridylium herbicide.Because of its good effect of weeding,paraquat is widely used in more than 120 countries in the world,and it plays an important ode in agriculture.Form 70s,its high toxicity has been reported in animals as w ell as in human,and we have no effective antidote.Once someone poisoned,the life will be in danger.It already confirmed that paraquat was a stable compound,it has long biological half-life in the soil,and can be easily absorbed by organism.Therefore with the increased usage of paraquat,the remaining in the environment and food material will bring tremendous influence to the mankind and the environment.Paraquat poisoning in the early phase can cause acute lung injury(ALI) or acute respiratory distress syndrome(ARDS).Patients usually die of multi-organ function failure or respiratory failure.The undermining pathogenesis is unclear.There is no ideal therapy at present.Modem research assume that neutropil is the main inflammatory cell in the progress.It adheres to endothelial,releases oxyradical and various Proteases which injury the lung.Ulinastatin is an broad-spectrum protease inhibitor.It can stabilize the lysosomal membrane,inhibit the activity of elastase,disintegrate fibrin,IL-6,IL-8 and eliminate oxyradical.Objective To establish rats model of acute lung injury by paraquat and study the protective effect of ulinastatin(UTI) against paraquat(PQ)-induced acute lung injury(ALI) and its mechanism.Materials and Methods1 PreparationsAll 45 healthy adult Wister rats were randomizedly assigned into three groups and there were twenty rats in each group:normal control group,PQ group,UTI group.Lung injury was observed at the times of 8,24,48 and 72h respectively.①NS group(n=5):the same volume of 0.9%saline solution was orally administered to rats.②PQ group(n=20):20%paraquat(30mg/kg) was given by the oral cavity at the first day.③UTI group(n=20):ulinastatin(100 000u/kg) was injected into peritoneum at 30 minutes after oral administration of PQ.2 MeasurementsVenous blood was obtained from heart under anesthesia.Isolated right lung tissue and collected left bronchoalveolar lavage fluid(BALF).Protein content in BALF and wet/dry weight(W/D) were measured.The quantity of WBC,the percentage of PMN,the content of MDA,GSH-Px and SOD activity in blood and BALF were routinely measured.Right lung tissue were observed through light microscope(LM).3 Statistical MethodsAnalysis was performed for statistical analysis with aid of SPSS 11.5 software.All data were expressed as mean±standard error of the mean..P values less than 0.05 were considered statistically significant.Results1 wet/dry weight(W/D):W/D was increased after the administration of paraquat.PQ group or UTI group compared with NS group at the same time had significant difference.W / D was lower in UTI group than that in PQ group(P＜0.01).2 Protein contents in BALF:protein contents in BALF was increased after the administration of paraquat.PQ group or UTI group compared with NS group at the same time had significant difference(P＜0.01).Protein contents in BALF was obviously lower in UTI group than that in PQ group(P＜0.01).3 Quantity of WBC and the percentage of PMN in plasma and BALF:quantity of WBC and the percentage of PMN in plasma and BALF was increased after the administration of paraquat.PQ group or UTI group compared with NS group at the same time had significant difference(P＜0.01).Quantity of WBC and the percentage of PMN in plasma and BALF F was obviously lower in UTI group than that in PQ group(P＜0.05).4 The results of GSH-Px,SOD and MDA in plasma or BALF4.1 Compared with control group,the level of MDA in PQ group increased significantly both in plasma and BALF(P＜0.01);SOD and GSH-Px in plasma were all decreased(P＜0.01).The activities of SOD and GSH-Px in BALF were all decreased,but SOD showed increase 48h later(P＜0.01).4.2 Compared UTI group with PQ group,the MDA level decreased both in plasma and BALF(P＜0.05),the SOD and GSH-Px activities were significantly increased as well(P＜0.01).Conclusions1 Oral administration of PQ caused acute pulmonary impairment with MDA increasing and SOD,GSH-px activity decreasing in plasma and BALF.The imbalance of oxidation and anti-oxidation resulting from hyperproduction of free radical is the causation of acute lung injury induced by paraquat poisoning. 3The percentage of PMN was increased obviously during early stage of acute lung injury induced by paraquat.The PMN may play an important role in the pathogenesis of paraquat-inducded acute lung injury.2 After therapy though peritoneal injection of PQ,the pulmonary exudation and PMN cells decreased,MDA content declined,SOD,GSH-Px levels elevated.Our study shows that UTI has effect of anti-inflammation and anti-oxidation.UTI has obviously therapeutic effect in paraquat poisoning.