| BackgroundAcute paraquat can cause multiple organ damage,and lung is the main target organ,which can cause early acute lung injury and later pulmonary fibrosis.The formation of pulmonary fibrosis is associated with various inflammatory mediators and cytokines,among which TNF-a and TGF-β play an important role.Etanercept as a kind of cytokine antagonists,can inhibit the activity of TNF-a and reduce the case fatality rate of acute paraquat poisoning in theory.However,the impact of Etanercept on pulmonary fibrosis in rats caused by acute paraquat poisoning is still not clear.ObjectiveTo explore the effect of Etanercept on the pulmonary fibrosis of acute paraquat poisoning rats,and to provide new ideas for the treatment of acute paraquat.Methods120 healthy SD(12-15 weeks old,250-300 weight)male rats were randomly divided into three groups:model group,intervention group and control group,18 rats in each group.The rats of the model group were infected with a dose of paraquat 80mg/kg and diluted to 1ml by oral perfusion.The rats in Intervention group were given etanercept with 0.6mg/kg subcutaneously,twice a week,after 1ml of paraquat were infected.The rats in Control group were given by gavage with 1ml sterile water for injection.the rabbits change of rats in each group were observed daily.3 rats of each group were killed on day 1,3,7,14,21,28 to extract lung issues.The lung issues were stained by hematoxylin-eosin,the expression of TNF-a and TGF-3 were detected by immunohistochemical method and detected the hydroxyproline concentration.ResultsIn this study,rats in the control group had normal life status,normal weight and normal lung function.In the model group,the weight of the rats was significantly reduced,the mental state was depressed,the activity decreased,the food intake was reduced,and the general observation of the lung was gradually showing the bleeding point,the stasis,the elasticity and the hardness.The rats in the intervention group also showed weight loss,eating and drinking less,but they were less than those of the model group in every time points,and the lung lesions were generally observed at different time points.Basic normal control group rats alveolar structure,lung interval is only a small amount of inflammatory cells exudation,model group rats with paraquat poisoning disease progress,alveolar inflammation and lung fibrosis degree aggravating gradually,intervention group rats alveolar inflammation and lung fibrosis at each time point than model group.With the extension of poisoning time of rats model group increased expression of TNF-a,maximum in 7 days,after gradually reduce,but expression of TNF-a are higher than the control group in every.time point,P<0.01,there are significant difference statistically;The expression of TNF-a in the intervention group was lower than that in the model group,and the P<0.05 in day 3,7,14,21 and 28,and the difference was statistically significant.Comparison between various points in three groups,Fd1=76.46,Fd3 = 14.66,Fd7 = 193.89,Fd14=167.22,Fd21 = 67.81,Fd28 = 69.8,in day 1,3,7,14,21,28,P<0.01,the difference was statistically significant.In model group,the expression of TGF-β was also gradually rise with the extension of poisoning,the 14th day was the peak,then reduce gradually,but the TGF-β expression were higher than the control group in each time point,P<0.01,with significant difference statistically.The expression of TGF-β in the intervention group was lower than that in the model group,and the P<0.01 in the 3,7,14 and 21 days,and the difference was statistically significant.Comparison between various points in three groups,Fd1= 14.25,Fd3 = 21.48,Fd7 = 41.05,Fdl4 = 338.81,Fd21 = 30.81,Fd28 = 22.44,in day 1,3,7,14,21,28 days,P<0.01,the difference was statistically significant.The content of hydroxyproline also increased gradually during the poisoning,until to the highest point of the 28th day,indicating that the degree of pulmonary fibrosis of the rats was gradually increased.The content of hydroxyproline in the model group was higher than that in the control group,and the P<0.05 in day 3,7,14,21and28,and the difference was statistically significant.The content of hydroxyproline in the control group was lower than that in the model group,and the P<0.05 in day7,14,21 and 28,and the difference was statistically significant.Among the three groups,Fdl = 2.08,Fd3 = 3.54,Fd7 = 9.38,Fd14 = 18.86,Fd21 = 56.34,Fd28 = 49.49,7,14,21,28 days,P<0.01,and the difference was statistically significant.ConclusionEtanercept can inhibit the lung injury and the formation of pulmonary fibrosis,and reduce the mortality of paraquat poisoning. |
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