Pei Xiao-yang, Feng Jian-zhang, Qian Wei-min, Yu Xi-yong, Wu Shu-lin, Yang Ping-zhen, Liu Yuan
Department of Cardiology, Guangdong Provincial Cardiovascular Institute, Guangzhou 510100, China.
Di Yi Jun Yi Da Xue Xue Bao. 2004 Apr;24(4):400-3.
To investigate the effects of C-type natriuretic peptide (CNP) gene transduction on neointimal hyperplasia and endothelial function after angioplasty.
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.
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).
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.
探讨C型利钠肽（CNP）基因转导对血管成形术后新生内膜增生及内皮功能的影响。
84只兔分为3组，每组28只，即正常对照组、碱性磷酸酶基因转导组和CNP基因转导组。后两组兔在实验前7天给予高胆固醇饮食，然后通过损伤髂动脉建立再狭窄模型，并经逆转录病毒载体进行特定基因转移。正常对照组兔给予正常饮食。在给予高胆固醇饮食前及处死前，分别采集2 ml静脉血样检测血脂和血清CNP浓度。在基因转导的两组中，取损伤的兔髂动脉进行离体血管环张力测试、组织学和病理学检查以及CNP免疫组织化学分析。用图像分析系统测量管腔面积、新生内膜厚度、新生内膜面积、内膜与中膜面积比值。
两个基因转导组在手术前后同一时间点的血脂和血清CNP浓度无显著差异。在CNP基因转导组中，无论是否进行L-精氨酸预处理，血管环的内皮依赖性舒张功能均较其他两组显著改善（P<0.01），而三组之间的非内皮依赖性舒张功能变化不大（P>0.05）。用左旋甲基精氨酸（LMMA）预处理后，血管环对乙酰胆碱（Ach）的舒张功能较差。在CNP基因转导组检测到基因转移部位的CNP基因表达，球囊损伤后2周，两个基因转导组的新生内膜厚度、新生内膜面积及内膜与中膜面积比值均明显增加，但CNP组的测量值明显较低（P<0.01）。
CNP基因可在血管损伤部位成功转移并有效表达，以减少血管成形术后的增生并显著改善内皮功能。
