Protective Effect Of Citeulline On The Injury Of Heart,Liver And Kidney In Septic Rats

Objective : To investigate the organ injury in rats with sepsis,and the protective effect of citrulline on blood composition and organs(including heart,liver and kidney)in rats with sepsis,discuss the new ideas for the protection of organ injury in clinical sepsis.Methods: 136 healthy adult male Wistar rats were randomly divided into normal group with(group Normal,n=8),sham operation group(Group sham,n=8),citrulline control group(group Cit,n=8),normal saline control group(group NS,n=8),the CLP model of sepsis group(CLP group n=52,CLP),model plus citrulline gavage treatment group(group CLP+Cit,n=52),Cit group and CLP+Cit group rats were given preoperative citrulline continuous intragastric administration of 7D,the dose of 200mg/d,NS group rats were given saline gavage at a dose of 7D,200mg/d;CLP group and CLP+Cit group the implementation of cecal ligation and puncture operation model(cecal ligation and puncture,CLP),according to the model after the rats were killed at the time,the separation of 6h,12 h,24h three time point subgroups.The rats of each groups were sacrificed at the scheduled time,the rat blood,heart,liver,andkidney were collected.The rat heart,liver and kidney tissues were examined by HE staining to observe the pathological changes.The rat blood were taken for blood test,determination of leukocyte count,erythrocyte count,hemoglobin,platelet count,neutrophils,neutrophil percentage and the blood biochemical indexes including creatine kinase(CK),creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),a-hydroxybutyrate dehydrogenase(HBDH),r-glutamyltranspeptidase(?-GT),aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(AKP),urea(BUN),creatinine(SCr),creatinine clearance rate(Ccr),Cystatin C(Cys C),high sensitive C-reactive protein(hs-CRP).The levels of NO,iNOS in blood and the levels of SOD and MDA in the heart,liver and kidney tissues were measured in each group.The statistical analysis of the data using statistical software SPSS 17,P < 0.05 bilateral difference was statistically significant.Results: The experimental results show that the white blood cell count,neutrophils,neutrophil percentage in CLP+Cit groups were lower than that in CLP groups(P < 0.05);the red blood cell count,hemoglobin and platelet counts in CLP+Cit groups were higher than that in CLP groups,but there were no statistical differences(P > 0.05);In 6h,12 h,24h three time points,the level of serum NO in CLP 6h and 12 h Subgroup were significantly higher than that in CLP+Cit group(P < 0.05).The serum iNOS activity in CLP groups were higher than that in CLP+Cit groups,but there were no statistical significance between the two groups(P > 0.05);The SOD activity of heart,liver and kidney tissue in CLP+Cit 12 h,24h subgroup were higher than that in CLP subgroup(P < 0.05),while the level of MDA in CLP+Cit subgroup rats tissue were lower than that in CLP subgroup(P < 0.05).HE staining showed that a lot of inflammatory cells were infiltrated in the heart,liver and kidney cells and degeneration and necrosis happen in cells in CLP group in CLP group.However,such phenomenon was alleviated in CLP+Cit group.In addition,the level of serum CK,CK-MB,HBDB,ALT,AKP,SCr,hs-CRP in CLP+Cit 6h subgroup were lower than that in CLP group(P <0.05).The level of serum CK,HBDH,?-GT,ALT,AKP,BUN,SCr,Cys C,hs-CRP in CLP+Cit 12 h subgroup were lower than that in CLP group(P <0.05).The level of serum CK,HBDH,ALT,AKP,BUN in CLP+Cit 24 h subgroup were lower than that in CLP group(P < 0.05).While the level of serum Ccr in CLP+Cit 12 h and 24 h subgroup was higher than that in CLP group(P < 0.05).Conclusion: 1.Supplement of citrulline protects the heart function,decreased the serum CK,CK-MB,LDH,HBDH in sepsis rats.2.The supplement of citrulline protects the liver function,reduce the lever of serum ALT,AST,?-GT,AKP level in sepsis rats.3.The supplement of citrulline protects the renal function,reduce the lever of serum BUN,SCr,Cys,C,hs-CRP concentration in sepsis rats.4.The supplement of citrulline improve the antioxidant capacity in heart,liver,kidney tissue,and decrease the concentration of NO in serum,reduce oxidative stress organs injury in sepsis rats.