Research On Prevention Of Everolimus Associated With Pravastatin On Allograft Angiopathy In Rats

Objective To investigate the prevention of everolimus and pravastatin respectivelyand their associated effect on allograft angiopathy in rats, then discuss their potentialmechanism of action and possible synergistic action.Methods The establishment of allograft model was used with carotid transplantationin rats.60rats were randomly classified into four groups: the control group (A),pravastatin-treated group (B), everolimus-treated group(C) and combination-treatedgroup (D). At0,1,4,8weeks after transplantation, the lipoprotein profile and NOcontent in blood serum were detected, also the grafts were harvested to observed theregional changes in the intimal layers by light microscopy and the expression ofTNF-α, IL-1β, eNOS, MHC-Ⅱ, VCAM-1, PCNA, CD4+T cells in allografts byimmunohistochemistry.Results There was a less intimal thickness in both everolimus group and pravastatingroup, and the reduction was most apparent in the combination–treated group.Pravastatin lower the level of cholesterol while the effect of everolimus was opposite.Pravastatin raised the concentration of NO in blood serum. Also pravastatin inhibitthe expression of TNF-α, IL-1β in transplanted artery. Everolimus inhibit theexpression of VCAM-1, PCNA in transplanted artery, inhibit SMC’s proliferation.There was a synergistic decrease in the expression of MHC-Ⅱ and CD4+T cells inthe condition of a combination of everolimus and pravastatin.Conclusion The prevention of everolimus and pravastatin on allograft angiopathy wassignificant at the dose of this experiment, and the effect was most obvious in acombination of both drugs. Pravastatin may exert its function to prevent allograftangiopathy by the mechanism of cholesterol-lowering, the increase expression ofeNOS and secretion of NO, direct anti-inflammatory effect, commissural inhibitionwith everolimus on the expression of TNF-α, IL-1β, MHC-Ⅱ, VCAM-1, PCNA andCD4+T cells and the proliferation of SMC.