Role of the Antisense and Decoy Oligonucleotide of Nuclear Factor-κB in the Vessel Stenosis and Neointima Formation in Balloon-injured Rat Artery

Aim To examine the effect of the antisense or/and decoy oligonucleotide of nuclear factor κB (NF κB) on balloon injured intercellular adhesive molecular 1 (ICAM 1) and monocytes chemotactic protein 1 (MCP 1) in the carotid artery of rats in vivo. Methods Sprague Dawley rats underwent balloon dilation injury of the left carotid artery. Rats was divided into 7 groups (n=18) and each group included 6 time points (6 hours and 1,3,5,7,14 days) (n=3). Uninjured artery of the same rat was used to be control. Results In model group, sense group and scramble group, vessel intima area, media area and intima/media ratio increased after 5 days and reached the maximum after 14 days. Whereas lumen area decreased with different time points. Antisense group, decoy group, antisense plus decoy group improved these observational index (P0.05). The effect of antisense plus decoy group was more obvious than that of antisense group and decoy group alone. ICAM 1 and MCP 1 mRNA expression were examined after 6 hours of artery injury, but not evident after 1 days. They increased expression continuously after 3,5 and 7 days and decreased after 14 days. Comparing with model group, sense group and scramble group, antisense group, decoy group and antisense plus decoy group all lowered ICAM 1 and MCP 1 mRNA expression in every time point (P0.05). Immunohistochemistry studies revealed ICAM 1 and MCP 1 protein were positive stain within six time points and maximal after 14 days. In antisense group, decoy group and antisense plus decoy group, ICAM 1 and MCP 1 protein synthesis decreased in every time point comparing with model group, sense group and scramble group. Western blot studies showed NF κB p65 was disperse positive stain after 6 hours of injury and increased after 1 day and reached the peak, but protein expression was weak after 14 days. Antisense group, decoy group and antisense plus decoy group treatment inhibited protein synthesis more significantly than those of model group, sense group and scramble group(P0.05). Conclusions NF κB modulated genes expression and protein synthesis of ICAM 1 and MCP 1; Celluar proliferation in vessel wall was dynamic change after balloon angioplasty injury; Antisense and decoy oligonucleotide of NF κB by local lipofectamine transfer inhibited NF κB activating genes modulation and the combined effect were remarkable than alone.