c-jun反义核酸对自体移植静脉内膜增生和ET-1水平的影响

目的 :观察反义c - jun核酸对自体移植静脉内膜增生及血管活性因子内皮素 - 1(ET - 1)的影响。方法 :选择 6 0只SD大鼠 ,等分为实验组和对照组 ,均行自体颈外静脉、腹主动脉移植手术 ,实验组移植静脉周围和血管吻合口周围应用反义c- jun核酸凝胶涂布 ;对照组仅行凝胶涂布。于手术时取静脉血 1ml,放射免疫分析检测血浆ET - 1的水平。术后 2周取出移植血管 ,分别行病理学、免疫组织化学检测移植血管内膜厚度 ,内膜平滑肌细胞数及增殖细胞核抗原和脱氧核糖核酸反映血管平滑肌细胞增殖情况的指标的表达情况。同时在另一侧颈外静脉取静脉血 1ml,仍采用放射免疫分析检测血浆ET - 1水平。结果 :移植静脉术后动脉化 ,管壁增存 ,血浆ET - 1水平升高 ,但转染c - jun反义核酸组移植血管内膜厚度及VSMC增殖均较对照组减少 ,PCNA和DNA阳性表达情况亦较对照组明显减少 ,血浆ET - 1水平升高幅度低于对照组。结论 :反义c - jun核酸可抑制VSMC分裂而减少VSMC的增殖 ,降低促进血管收缩和细胞增殖的ET - 1的表达 ,从而有效地抑制移植静脉内膜的过度增生。

Effect of Local Application of C-jun Antisense Olignucleotide on the Intimal Proliferation of Venous Autografts and Plasma ET-1 Levels

Objective To investigate the effect of c-jun antisense olignucleotide on the intimal proliferation of venous autografts and plasma endothelin-1 (ET-1) levels. Methods The external jugular vein was autografted into abdominal aorta in 60 rats. The anastomosis and vein graft were coated with glue gel containing c-jun antisense olignucleotide in the experimental group (n=30) while in the control group (n=30) plain glue gel without medication was applied. Plasma ET-1 levels from the blood sample obtained at the operative site were determined with RIA. Two weeks later, the autografted vein segments were removed and examined with conventional histologic as well as immunohistochemistry method for intima thickness, proliferation of vascular smooth muscle cell (VSMC) and quantity of proliferating cell nuclear antigen (PCNA) and desoxyribonucleic acid (DNA) in VSMC. Plasma ET-1 levels in blood from the opposite jugular vein were again measured. Results The venous intimal layers were thickened in all the specimens. However, the degree of intimal thickening and luminal stricture, the number of VSMC and expression of PCNA as well as the plasma ET-1 levels were significantly lower in the expression group where c-jun antisensc olignucleotide was applied (vs control group, P<0.01). Conclusion Local application of c-jun antisense olignucleotide was effective in reducing the intimal thickening of the autografted vein through inhibition of PCNA expression and VSMC proliferation. Intimal ET-1 synthesis was also expression decreased.