Research On Prevention Of Sirolimus Associated With Catopril On Allograft Angiopathy In Rats

Objective To investigate the prevention of sirolimus and catopril respectively and their associated effect on allograft angiopathy in rats,then dicuss their potential mechanism of action and possible synergistic action.Methods The establishment of allograft model was used with carotid transplantation in rats.60 rats were randomly classified into four according to being given different medicine:the controlled group (A),catopril-treated group (B),sirolimus-treated group (C) and combination-treated group (D).At 0,1,4,8 weeks after transplantation the NO content,the cholesterin,ALT,Cr in blood serum were detected, also,the grafts were harvested for observing the regional changes in the intimal layers by light microscopy and the expression of TNF-α,eNOS,TGF-β1,VCAM-1,PCNA,CD4+T cells in the allograft by immunohistochemistry.Results There is a less intimal thickness in both catopril-treated group and sirolimus-treated group,especially in the combination-treated group. Catopril can enhance the content of NO in blood serum;it can also inhibit the expression of TNF-α,eNOS,VCAM-1 and TGF-β1 in the allograft,inhibit SMC'S proliferation. There is a apparent decrease of CD4+T cells'infiltration in the transplanted artery of the combination-treated group.Conclusion The prevention of catopril and sirolimus on allograft angiopathy is significant at the dose of this experiment,and the effect is most obvious in a combination of both drugs. The combination of the both drugs may prevent CAV by the menchanism of lightening immune reaction,enhanced expression of eNOS and secretion of NO, direcred anti-inflammatory effect, inhibition on the expression of VCAM-1,TGF-β1 and the proliferation of SMC .