转导C型钠尿肽基因对血管成形术后新生内膜增生及内皮功能的影响

Effects of C-type natriuretic peptide gene transduction on neointimal hyperplasia and endothelial function after angioplasty]

OBJECTIVE: To investigate the effects of C-type natriuretic peptide (CNP) gene transduction on neointimal hyperplasia and endothelial function after angioplasty. METHODS: Eighty-four rabbits were divided into 3 equal groups, namely normal control group, alkaline phosphatase gene transduction group and CNP gene transduction group. The rabbits in the latter two groups were given high-cholesterol diet 7 d before the experiment, followed by establishment of restenosis models by injuring the iliac artery and the specified gene transfer via retroviral vectors. Those in the normal control group were fed with normal diet. Before high-cholesterol diet and killing respectively, 2 ml venous blood samples were taken for testing blood lipid and serum CNP concentration. In the two groups with gene transduction, the injured rabbit iliac arteries were harvested for ex vivo vascular ring tension test, histological and pathological examinations, as well as immunohistochemistry analysis of CNP. The lumen area, neointimal thickness, neointimal area, ratio of intimal to medial area were measured by image analysis system. RESULTS: There were no significant differences in blood lipid and serum CNP concentration between the two gene transduction groups at the same time points both before and after operation. In CNP gene transduction group, endothelium-dependent relaxation of the vascular rings was significantly improved in comparison with the other two groups (P<0.01), irrespective of L-Arg pretreatment, whereas endothelium-independent relaxation function varied little between the 3 groups (P>0.05). Poor relaxation function to Ach of the vascular rings was resulted after pretreatment with LMMA. CNP gene expression at the site of gene transfer was detected in the CNP gene transduction group and in 2 weeks after balloon injury, the neointimal thickness, neointimal area and ratio of the neointimal to tunica media area were markedly increased in the two gene transduction groups, but the measurements were significantly lower in CNP group (P<0.01). CONCLUSION: CNP gene can be successfully transferred and effectively expressed at the injured site in the blood vessels to decrease the hyperplasia and significantly improve endothelial function after angioplasty.