Protective Effect And Mechanisms Of Ethyl Pyruvate On Coagulation Disorders In Sepsis

Objective1.Application sepsis classic cecal ligation and puncture (CLP) to establish the mousedisseminated intravascular coagulation (DIC) in animal models to explore ethyl pyruvate(EP) the protective effect of sepsis coagulopathy.2. Dynamic observation of cecal ligation and puncture (cecal ligation Puncture CLP) sepsismodel mice blood high mobility group protein content the Bl (high mobility group boxlportein, HMGBl) of changes in lung tissue protein levels of pyruvate B the ester (EP)HMGBl, to explore the mechanism of action of ethyl pyruvate on sepsis, coagulationdisorders, provide a new theoretical basis for sepsis organ protection.MethodsThe the SPF grade Kunming (KM)135male mice were randomly divided into shamoperation group (sham), CLP-induced sepsis group (CLP group), acetone, ethylintervention group (EP group), n=45,The mice were observed at different time pointsafter eating, breathing, piloerection, diarrhea, discharge, sunken eyes, urine output survival,sandwich enzyme-linked immunosorbent assay (ELISA) testing immediately after,4hours,8hours,12hours,24hours,48hours,72hours7platelet (PLT) count, alanineaminotransferase (ALT), creatinine (Cr), prothrombin time (PT), activatedpartialthromboplastin time (APTT), fibrinogen (FIB), D-dimer, protein C (PC), highmobility group protein Bl (HMGB1), and were killed before sepsis score observedmicewith sepsis severity score, survival time, protein levels detected by Western blot in lungtissue HMGBl and lung, intestinal histopathology HE observed after.Results1. After observation for72h survival rate of sham group was100%, the EP group was60%,the the CLP group survival rate was10%(P <0.05). Compared with sham group, the PLT of mice in the EP group and CLP that of gradually decreased8hours after modeling, butthe PLT of EP group was significantly higher than the same point in time CLP group (P<0.05); with sham group compared to APTT, PT extend, but the EP group than in the CLPgroup was significantly longer time is shorter (P <0.05); compared with sham group ALT,Cr was significantly higher, but the EP group was significantly lower than the same pointin time CLP group (P <0.05). Light microscope CLP group, EP lung intestinal tissue canbe seen the obvious acute lung injury performance: congestion, edema, inflammatory cellinfiltration, varying degrees of micro-thrombosis, EP group than in the CLP group ofpathological damage is significantly reduced, and the intestinal lung injury score wassignificantly decreased (P <0.05).2. EP group and CLP group were observed for8hours FIB decreased to24hours to reachthe peak, but the EP group was significantly higher than the same point in time CLP group(P <0.05). EP group and the CLP group observed8hours after the D-Dimer wassignificantly increased to12hours to reach the peak, then gradually decreased, but the EPgroup was significantly lower than the same point in time CLP group (P <0.05). The CLPgroup12hours after the beginning of serum PC was significantly higher,48-hour peak andcontinuing to72hours, while the EP group was significantly higher in the12-hour PC, andsignificantly higher than the same point in time CLP group (P <0.05). The CLP groupfound in the serum HMGB1observed after8hours was significantly higher peak in12hours, and then began to decrease, the effect is sustainable over72hours, but the EP groupwas significantly lower than the same point in time CLP group (P <0.05). sham group atdifferent time points the mouse HMGBl proteins have a trace expression of the CLP groupEP group HMGBl protein from8hours began to express increased significantly, to12hours24hours48hours began to decline significantly but still higher than the sham group,EP group was significantly lower than the same point in time protein levels CLP group (P<0.05), but still higher than the sham group and a significant difference (P <0.05). Conclusions1.CLP mouse model can reflect similar to the clinical development of DIC process, can beused as a the DIC study of animal models. Ethyl pyruvate can significantly reduce theCLP-induced sepsis, coagulation disorders, increase the survival rate of sepsiscoagulopathy.2.Ethyl pyruvate can significantly inhibit septic mice HMGBl level; by inhibiting HMGBlto regulate fibrinolysis and coagulation system in order to effectively reduce t he the CLPinduction of sepsis coagulopathy.