Abstract： Objective To investigate the effects and possible mechanisms of antisense ERK2 gene therapy upon chronic allograft vasculopathy.Methods Adanti-ERK2 and Ad-LacZ were constructed using the Adeno-XTM expression system.Transplantation was performed using male Brown Norway(BN;RT1.An)as donors and male Lewis(LEW,RT11)rats as recipients.In the control group the allografts were subect to no intervention,in the Ad-LacZ group the allografts were transfected with Ad-LacZ before transplantation,and in the Adanti-ERK2 group the allografts were transfected with Adanti-ERK2 before transplantation.At day 60 after transplantation the aortic grafts and serum of recipients were harvested.GAPDH being served as the internal control.the ratio of expression of ERK2 and GAPDH(ERK2/GAPDH)was assessed by Western blotting;the thickness of the intima and media was detected and then the I/(I+M)was calculated;the proliferation and migration of vascular smooth muscle cells(VSMC)were assayed by immunohistochemistry;the level of PDGF-BB in the serum was determined by ELISA Results The I/(I+M)in control group an4 Ad-LacZ group was 84.1%and 79.9%,respectively,significantly higher than 13.7%in Adanti-ERK2 group (P＜0.05)which only presented endarteritis.In the thickening intima in control group and Ad-LacZ group,the BSMCs diffusely distributed and numerated as 71.3±9.2 and 76.4±11.3,respectively,significantly different from 34.8±5.3(P＜().05)in Adanti-ERK2 group.The level of PDGF-BB was 1075±70 pg/ml and 1 200±25 pg/ml in control group and Ad-LacZ group,respectively,significantly lower than 626±27 pg/ml in Adanti-ERK2 group.Conclusion Antisense ERK2 gene therapy can attenuate chronic allograft vasculopathy SO as to protect aortic allografts.The mechanism seems tO cotrelate with inhibition of proliferation and migration of VSMCs and down-regulation of the PDGF-BB expression.