The Effects Of Sivelestat Sodium On Early Inflammatory Reaction Of Rats With Smoke Inhalation Injury

BackgroundSmoke inhalation injury often leads to acute lung injury,and its treatment is extremely difficult.The mortality rate of acute lung injury caused by Moderate or severe inhalation injury can reach 30%,Although the level of general treatment has made great progress,there are still many stubborn cases which cannot be relieved by conventional treatment.At this time more effective and novel treatment needs to be excavated.Sivelestat sodium,as the first drug to treat acute lung injury,has entered into clinical research stage.The results of the study have proved that it has a certain therapeutic effect to treat acute lung injury.Although many domestic and foreign literatures have reported that sivelestat sodium has a different degree of protection of acute lung injury in animal injured models.But there is no reliable literature report on the specific therapeutic effect in the animal model of smoke inhalation injury.This study intends to adopt the sivelestat sodium to intervene in rats with smoke inhalation injury,and according to a number of detection indicators,to evaluate its effect on early inflammatory response,explore its potential therapeutic effects and explore its possible mechanisms of treatment.Objectiveto evaluate the inhibitory effect of sivelestat sodium on inflammatory factors 、tissue edema and pathological changes after smoke inhalation injury in rats.MethodsForty SPF male SD rats were divided into 5groups following random principles:normal control group(A)、injury group(B)、smoke inhalation group treated with10mg/kg sivelestat sodium group(C)、20mg/kg treatment group(D)、30mg/kg treatment group(E)and 8 rats each group.Use smoke generator to establish the model of smoke inhalation injury in rats.Afeter injured model established,the treatment groups were intraperitoneally injected sivelestat sodium 10mg/kg 、20mg/kg 、 30mg/kg separately,injured group was treated with the same volume physiological saline,normal control group was treated with nothing.After 24 hours,ELISA was used for detecting content of neutrophil elastase(NE)、myeloperoxidase(MPO)in serum,tumor necrosis factor-α(TNF-α)、interleukin-6(IL-6)both in serum and bronchoalveolar lavage fluid in each group,meanwhile measure the water content of lung tissue and observing their pathological changes by HE staining,measure and compare the thickness of alveolar septum.ResultCompared with control group,the levels of NE、MPO in serum,the levels of TNF-α、IL-6 both in serum and bronchoalveolar lavage fluid、water content of the lung tissue and thickness of alveolar septum were significantly higher in other groups(P < 0.05);Compared with injury group,the levels of NE、MPO in serum,the levels of TNF-α,IL-6both in serum and bronchoalveolar lavage fluid,water content of the lung tissue and thickness of alveolar septum were significantly lower in each treatment group(P <0.05);Compared with10mg/kg treatment group,the levels of NE 、 MPO in serum,the levels of TNF-α,IL-6 both in serum and bronchoalveolar lavage fluid,water content of the lung tissue and thickness of alveolar septum were significantly higher in 20mg/kg treatment group(P<0.05);Compared with 20mg/kg treatment group,the levels of NE、MPO in serum,the levels of TNF-α,IL-6 both in serum and bronchoalveolar lavage fluid,water content of the lung tissue and thickness of alveolar septum were significantly higher in 30mg/kg treatment grou(P<0.05);Conclusion1.Sivelestat sodium can inhibit the release of inflammation related active substances(such as NE、MPO、IL-6、TNF-α etc)in serum after smoke inhalation injury in rats,improve the edema of lung tissue,inhibit the inflammatory response in lung afterinjury and protect the injured lung tissue.2.In this experiment,the intervention effect of sivelestat sodium is not proportional to the dose,the 10mg/kg treatment group was better than treatment groups.