Protective Effect Of Low Molarculer Weight Heparin On Acute Renal Injury Induced By Sepsis In Rats

ObjectiveSepsis is an uncontralled systemic inflammatory response syndrome (SIRS), it may cause severe sepsis, septic shock and multiple organ dysfunction syndrome(MODS),the mortality rate has been maintained 50%-90%. Sepsis research has become hot point and difficulty issue in emergency and critical care medicine. Kidney is one of the most common organs affected by sepsis, and acute kidney injury (AKI) caused by sepsis has been considered to be independent risk factor of death, which mortality rate has been 74.5%. But its mechanism is not completely clear. Successful application of actived protein C with anticoagulation role in treatment of severe sepsis had resulted in universal recognition on protection role of traditional anticoagulatory drugs for sepiss and target organ injury induced by sepsis, which impulsed drug research like heparin with double-action of antiinflammation and anticoagulation. As one of the late-stage inflammatory cytokines, high mobility group box 1 protein (HMGB1) had been proved to play an important role in development and progress of sepsis. HMGB1 is a heparin binding protein,which is basis of heparin intervention of sepsis. In order to study mechanism of acute renal injury induced by sepsis and find effective protection methods for septic organ injury, we observe effects of low molecular weight heparin(LMWH) on renal HMGB1,plasma KIM-1,serum creatinine and explore the protection role and its mechanism of LMWH for acute renal injury induced by sepsis in rats.MethodsThe model of cecal ligation and puncture (CLP) was used to duplicate severe sepsis model. A total of 120 healthy male SD rats were randomly divided into three groups:sham operation group,CLP group and experimental group (low molecular weight heparin group),and each group has 40 rats. Five rats in each group were sacrificed at 3,6,12,24, 48 h after operation.Renal tissue express of HMGB1 mRNA and protein,plasma KIM-1, serum creatinine in all rats were measured by Reverse serum creatinine in all rats were transcription-polymerase chain reaction (RT-PCR),Western blot, Enzyme-linked immunosorbent assay (ELISA) and biochemical assay. Septic severity score and survival time were recorded.Results1. Septic severity score at 12 h,24 h,48 h after operation in experimental group were significantly higher than sham-operation group(P<0.05),but lower than CLP group(P> 0.05). The half survival time were significantly lower than sham-operation group(P< 0.05),but higher than CLP group(P<0.05).2.The expression of HMGB1 mRNA and protein at 12 h,24 h,48 h after operation in experimental group were significantly higher than sham-operation group(P<0.05),but lower than CLP group(P>0.05).3.Plasma KIM-1 at 6 h,12 h,24 h,48 h after operation in experimental group were significantly higher than sham-operation group(P<0.05),but lower than CLP group(P> 0.05).4.There is no difference in serum creatinine between experimental group and sham-operation group at3h,6 h,12 h,24 h,48 h after operation(P>0.05). Serum creatinine at 24 h,48 h after operation in experimental group were significantly lower than CLP group(P<0.05).ConclusionThe expression of HMGB1 mRNA and protein,plasma KIM-1 were significantly increased in septic rats. Plasma KIM-1 may be important indice in diagnosis of early AKI caused by sepsis.Low molecular weight heparin may effectively improve symptom,increase survival time,reduce septic severity score, HMGB1 and KIM-1. Low molecular weight heparin may play roles in renal protection in sepsis.