The Study On Prevention Of Leflunomid Associated With L-arginine On Allograft Angiopathy In Rats

Objective To investigate the prevention of Leflunomid and L-arginine respectively and their associated effect on allograft angiopathy in rats, and discuss 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 groups: the control group (A), L-Arg-treated group(B), LFM-treated group(C) and combination-treated group(D). At 0,1, 4, 8 weeks after transplantation, the lipoprotein profile and NO content,ALT,Cr in blood serum were detected, also the grafts were harvested to observed the regional changes in the intimal layers by light microscopy and the expression of eNOS,VCAM-1,TGF-β1,TNF-α,PCNA,CD4+ T cells in allografts by immunohistochemistry .Results There was the least intimal thickness ,the highest level of NO in blood serum ,the most expression of eNOS in transplanted artery, the least expression of PCNA VCAM-1,TGF-β1,TNF-α,and the expression of CD4+ T cells in group D.The opposite is group A.And group B and C are better than group A .( P<0.05) Conclusion The prevention of L-Arg and LFM on allograft angiopathy was significant at the dose of this experiment, and the effect was most obvious in a combination of both drugs. L-Arg may exert its function to prevent allograft angiopathy by the mechanism of the increase expression of eNOS and secretion of NO, indirect anti-inflammatory effect, commissural inhibition on the expresstion of VCAM-1,TGF-β1,TNF-α,PCNA and CD4+ T cells and the proliferation of SMC.