The inhibition of intimal hyperplasia in vascular grafts by slow-releasing rapamycin applied on the adventitia: an experimental study

Objective To establish a model of rabbit PTFE artificial vascular grafts at infrarenal abdominal aorta and to investigate the mechanism of re-stenosis inhibition by rapamycin.Methods Eighteen healthy New Zealand male rabbits weighted 2.5~3.0 kg were randomly divided into 3 groups to establish models of PTFE artificial vascular graft at abdominal aorta.Group A: the grafts accepted no management;group B: 0.5ml of 20% pluronic F-127 gel was locally applied on adventitia and anastomosis site of the graft;group C: 0.5ml 20% pluronic F-127 gel containing 0.5mg rapamycin was locally applied on adventitia and anastomosis site of the graft.The grafts were acquired after one month.Histomorphological method was used to detect the intimal hyperplasia of the specimen.Electronic imaging system was used to measure the thickness of intima and media of the grafts followed by calculating the degree of intimal hyperplasia(thickness of intima/thickness of media).α-actin,PCNA and p27kip1were investigated by using immunohistochemistry.Data were analyzed by using SPSS13.0 statistics software,and were expressed as mean ± SD.Results One month after the operation,the intima in group A and B thickened obviously as compared with that in group C(P0.05).Immunohistochemically,α-actin expressed in the hyperplastic intima,similar to the α-actin expression in smooth muscle cells of blood vessels.Immunohistochemistry for PCNA and p27kip1demonstrated that they were stained in cell nuclei,and were expressed in the thickened intima in grafts from the 3 groups.The expressions of α-actin and PCNA were lower in group C than in groups A and B(P0.05),while the expression of p27kip1was higher in group C than in groups A and B(P0.05).No significant differences in the above parameters were found between groups A and B(P0.05).Conclusion External application of rapamycin mixed with pluronic F-127 gel on graft adventitia can effectively inhibit the hyperplasia of vascular smooth muscle cells.The mechanism of re-stenosis inhibition by rapamycin may relate to the increase of p27kip1 expression and inhibition of cell proliferation cycle in vascular graft.