关键词: 骨形态发生蛋白2基因, 纳米粒子, 移植

Abstract: Abstract:Objective  To investigate the inhibitory effect of bone morphogenetic  protein 2(BMP-2) gene transfection mediated by nanoparticles (NP) on proliferation of vascular smooth muscle cells (VSMC) in rat vein grafting model,and to provide a new method to prevent restenosis.Methods The VSMC were transduced in vitro with NP BMP-2 DNA complex  prepared with PLGA and used as BMP-2-PLGA  group，meanwhile simple PLGA group and control group were set up.The cell proliferation was determined by flow cytometry.Autogenous vein graft models were established in 72 rabbits by transplanting internal branch of jugular vein to carotid artery,then divided into BMP-2 group,empty vector group and simple graft control group.The grafted veins were harvested at 3,7,14 and 28 d respectively after operation.The thickness of vascular inner membrane was detected with Verhoeff staining.The exogenous BMP-2 protein expression in veins was determined by Western blotting.The expressions of proliferating cell nuclear antigen (PCNA) and BMP-2 were detected by immunohistochemistry.Results Compared with control group, the inhibitory rate of cell proliferation and apoptotic rate  in BMP-2-PLGA  group  were  increased obviously(P<0.05) and the cell cycle was arrested in G1 phase（P<0.05）.Compared with empty vector group and simple graft control group,the thickness of vascular inner membrane  in BMP-2 group was decreased（P<0.01）,but  there was no significant difference between empty vector group and simple graft control  group.Compared with empty vector group and simple graft control group,the BMP-2 protein expressions in rabbit vein graft tissue in BMP-2 group 3,7,14 d after operation were significantly increased(P<0.05);the PCNA expressions were significantly decreased 7-28 d after operation(P<0.05);but there was  no significant difference between empty vector  group and simple graft control group.Conclusion Expression　of  BMP-2 gene  can prevent intimal hyperplasia (IH) and VSMC proliferation and it also can promote the apoptosis  of VSMC cultured in vitro.

Key words: bone morphogenetic protein-2 gene, nanoparticles, graft