| Objective:To investigate the effects and mechanism of heme oxygenase-1(heme oxygenase-1,HO-1)in DA to Lewis rat liver transplantation acute rejection model.Methods:36 male DA rat used as donors were randomly divided into 3 groups:Group A injected via vena dorsalis penis with 5ml/kg 0.9%NaCl; Group B injected via vena dorsalis penis with 5ml/kg cobalt-protoporphyrin(CoPP),heme oxygenase-1 inducer;and Group C injected via vena dorsalis penis with 5ml/kg zinc-protoporphyrin(ZnPP), heme oxygenase-1 inhibitor before livers were harvested.After transplantation,recipients were daily given the above treatments.6 recipients in each group underwent collection of blood and liver tissues 7 days after transplantation to detect the changes of serum enzymes (alanine aminotransferase,ALT;total bilirubin,TBIL)and the grafts histology.The expressions of HO-1 mRNA,Foxp3 mRNA and protein in the transplanted livers were detected by RT-PCR.The other 6 recipients in each group were used to observe the survival time.Results:The survival time of Group B(29.83±1.40d)was significantly longer than that of Group A(13.00±0.52d,P=0.000<0.01)and Group C (11.67±0.42d,P=0.001<0.01).The values of ALT and TBIL of Group B were significantly lower than those of Group A and C(all P<0.01).The histological manifestation of the grafts rejection in group A and C were severe than group B.HO-1 mRNA and Foxp3 mRNA expressions were only expressed in trace amount in the livers of normal DA rats,expressed in a small amount in the transplanted livers of Group A.The expressions of HO-1 mRNA,Foxp3 mRNA in the transplanted livers of Group B were significantly higher than those of Group A,and the expressions of HO-1 mRNA,Foxp3 mRNA of Group C were not significantly different from those of Group A.The expressions of HO-1 and Foxp3 protein were as the same.Conclusion:Continuous overexpression of HO-1 alleviated the reaction of acute rejection in liver transplantation.This effect depends,at least in part,on HO-1-mediated Foxp3 activation. |