Effect of anti-PMN serum treatment on D-GalN-induced ALF rats
ZHAO Xin;SHI Xiao-lei;MA Hu-cheng;DING Yi-tao;Department of Hepatobiliary Surgery,the Affiliated Drum Tower Hospital of Nanjing University Medical School;
Objective To investigate changes in the neutrophils in rats with D-galactosamine(D-GalN)-induced acute liver failure(ALF)and to explore the therapeutic effect of interventions treatment of neutrophils on ALF.Methods Liver function,the expressions of inflammatory cytokines TNF-αand IL-1β,and the changes of neutrophils in the peripheral blood and the liver were observed in rats with D-GalN(intraperitoneal injection)-induced ALF.SD rats were randomly divided into three groups when treated with intervention of neutrophils:control group,ALF group(intraperitoneal injection of D-GalN),and treatment group(intravenous injection of anti-PMN serum via tail vein 24 h before modeling).Biochemical analysis was used to detect serum ALT,AST,TBIL and blood ammonia.Hematology analyzer was applied to analyze the number and percentage of peripheral blood neutrophils.The number of neutrophils in the liver was evaluated by immunohistochemistry.Liver RT-PCR was adopted to detect the mRNA expression of inflammatory cytokines TNF-αand IL-1β.Results We found that6 h after D-GalN injection,serum ALT,AST,TBIL and blood ammonia in ALF rats were significantly increased(P0.05).The mRNA expression levels of inflammatory cytokines TNF-αand IL-1βin the liver reached the peak at 6 h after modeling(P0.001),and it was still notably higher at 24 h than before modeling(P0.001).The number and percentage of peripheral blood neutrophils and the number of neutrophils in the liver were all markedly increased 12 h after modeling(P0.001),and the increase continued at least until 24 h(P0.001).24 h after intravenous injection of anti-PMN serum via tail vein,ALF rats had a distinct decrease in the number of peripheral blood neutrophils and neutrophils in the liver 24 h after modeling(P0.001).Meanwhile,serum ALT,AST,TBIL and blood ammonia were all greatly decreased compared with those in ALF group(P0.05);a significant reduction of hepatocyte apoptosis was observed.Also,the expressions of TNF-αand IL-1βin the liver were remarkably decreased after treatment(P0.05).Conclusion Neutrophils accumulated in peripheral blood and liver of rats with D-GalN-induced ALF.The treatment of anti-PMN serum may have a therapeutic effect on liver function and immune microenvironment in ALF rats.
【Fund】： 国家自然科学基金资助项目(No.81170418);; 江苏省自然科学基金资助项目(No.BK20131084);; 中科院战略先导计划(No.XDA01030602)~~
【CateGory Index】： R575.3
【CateGory Index】： R575.3