Empirical Study Of HMGB1Expression And Effect Of Ulinastatin Of Rats With Acute Lung Injury Induced By Cecal Ligation And Puncture

Acute lung injury(ALI) is a clinical syndrome characterized by refractory hypoxemia andrespiratory embarrassment,related to high morbidity and mortility,which can be inducedby sepsis,shock,major operations and severe wounds.Acute respiratory distresssyndrome(ARDS)is the most serious syndrome of ALI.AS a inflammatory mediator andcytokine, high mobility group box1protein(HMGB1) is the key point to activate and keepthe inflammatory response.Inflammatory factor play an important role in the developmentof ALI.Previous studies showed that ulinastatin(UTI) can reduce the mortality of ALI,butthe mechanisms have not been established.this study is to research the protective effect andunderlying molecular mechanism of UTI in a rat model of cecal ligation and puncture(CLP)induced acute lung injury(ALI).Part Ⅰ The7days survival rate observation of acute lung injury rats induced bycecal ligation and puncture.Objective To observe whether UTI can reduce the mortality of ALI induced by cecalligation and puncture.Methods A total of30male SD rats were randomly divided into three groups: shamgroup(control group), CLP group,CLP+UTI group(UTI group),each group had10rats.Saline and UTI(100,00U/kg)were intravenously injected30min after CLP in CLP andUTI group,respectively.Results The7days survival rate of CLP group is50%,the7days survival rate of UTIgroup is7%, the7days survival rate of contro group is100%. The7days survival rate ofUTI group is higher than the CLP group,and has a significant difference (P <0.05).Conclusions UTI can improve the7days survival rate of CLP induced ALI ratssignificantly.Part Ⅱ Empirical study of HMGB1expression and effect of ulinastatin of rats withacute lung injury induced by cecal ligation and punctureObjective To research the protective effect and underlying molecular mechanism ofulinastatin(UTI) in a rat model of cecal ligation and puncture(CLP) induced acute lung injury(ALI) by observe the changes of HMGB1expression.Methods A total of120male SD rats were randomly divided into three groups: shamgroup(control group), CLP group,CLP+UTI group(UTI group),40rats in CLP group weredivided into4time point groups(6h,12h,24h,48h), each time point group had10rats. UTIgroup is same to CLP group,the control group had40rats. Saline andUTI(100,00U/kg)were intravenously injected30min after CLP in CLP group and UTIgroup,respectively.Then,samples were collected for further analysis at four timepoints(6h,12h,24h,48h).Results UTI group rats had less amelibrated alveolar epithelial cell and morphologicdamage than CLP group,and the lung tissue ultrastructure damage were also less than CLPgroup.The lung injury score of UTI group at48h time point was lower than CLP groupsignificantly(P <0.05). The lung tissue HMGB1mRNA expression of control group wasobviously lower than CLP group and UTI group (P <0.05). The lung tissue HMGB1mRNA expression of CLP group at12h,24h,48h time points were obviously higher thanUTI group (P <0.05),the lung tissue HMGB1concent of UTI group was significantlylower than CLP group at each time point(P <0.05);the HMGB1level in the serum of CLPgroup was significantly higher than UTI group and control group at each time point(P<0.05). The HMGB1level in the BALF of UTI group was obviously lower than CLPgroup at each time point(P <0.05).Conclusions HMGB1take part in the development of acute lung injury,UTI exerted aprotective effect against CLP induced ALI by suppressing the expression of HMGB1.