Li Dan-Yang, Zhao Kui, Zhou Jun-Fu, Chen Peng, Li Wei
Second Affiliated Hospital, College of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou 310009, Zhejiang, China.
Biomed Environ Sci. 2004 Dec;17(4):442-51.
To explore the changes of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and angiogenesis, and the effects of bFGF, angiotensin converting enzyme inhibiter(ACEI) benazepril on the angiogenesis in acute myocardial infarction (AMI) model of rabbits, and to provide a probable evidence for the treatment of AMI.
AMI model was established by ligating anterior descending branch of coronary artery of Japan-Sino hybridization white rabbits. The postoperative rabbits were randomly divided into 6 groups and each group was treated with different drugs. Groups 1 and 2 were treated with normal saline (NS) for 28 and 14 days (d), group 3 and 4 with bFGF for 28 and 14 d, groups 5 with benazepril for 14 d, and group 6 with benazepril and bFGF for 14 d respectively. The rabbits were killed on the 14th or 28th d and their hearts were excised, sectioned and stained with HE, Masson trichrome to observe VEGF, bFGF and CD(34) under a microscope, which were quantified with a computer-assisted morphometry.
Compared with group 1, the granulation tissue of infarction zone (IZ) in group 2 freshened up, and the capillary density (CD) in IZ was increased (P = 0.002). The CD in the IZ as well as VEGF and bFGF in groups 3 and 4 were increased respectively (P = 0.011-0.037). In group 5 the changes of VEGF and bFGF were not found in the IZ and the border zone (BZ) while CD was significantly increased (35.4% and 25.6%, P = 0.036 and 0.037). Compared with group 2, the CD in the IZ and BZ of group 6 was significantly increased (63.4% and 44.3% P = 0.007 and 0.007), meanwhile VEGF and bFGF were increased. Compared with group 5, only VEGF was increased.
Intravenous bFGF may increase VEGF and bFGF significantly, thus promoting the angiogenesis in the IZ and BZ in cardiac infarction as VEGF and bFGF are the potent angiogenic growth factors. Benazepril may promote angiogenesis in the IZ and BZ in cardiac infarction, but its mechanism is irrelative to the expression of VEGF and bFGF. The combination of benazepril and bFGF may promote, to some extent, the expression of VEGF and bFGF, but their effect on angiogenesis has not been found.
探讨血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）及血管生成的变化，以及bFGF、血管紧张素转换酶抑制剂（ACEI）苯那普利对兔急性心肌梗死（AMI）模型血管生成的影响，为AMI的治疗提供可能依据。
通过结扎日本大耳白兔冠状动脉前降支建立AMI模型。术后将兔随机分为6组，每组给予不同药物治疗。第1组和第2组分别用生理盐水（NS）治疗28天和14天，第3组和第4组用bFGF治疗28天和14天，第5组用苯那普利治疗14天，第6组用苯那普利和bFGF治疗14天。于第14天或28天处死兔，取出心脏，切片，进行HE、Masson三色染色，显微镜下观察VEGF、bFGF及CD34，并采用计算机辅助形态计量学进行定量分析。
与第1组相比，第2组梗死区（IZ）肉芽组织更新，IZ毛细血管密度（CD）增加（P = 0.002）。第3组和第4组IZ的CD以及VEGF和bFGF分别增加（P = 0.011 - 0.037）。第5组IZ和边缘区（BZ）VEGF和bFGF未见变化，但CD显著增加（35.4%和25.6%，P = 0.036和0.037）。与第2组相比，第6组IZ和BZ的CD显著增加（63.4%和44.3%，P = 0.007和0.007），同时VEGF和bFGF增加。与第5组相比，仅VEGF增加。
静脉注射bFGF可显著增加VEGF和bFGF，从而促进心肌梗死IZ和BZ的血管生成，因为VEGF和bFGF是有效的促血管生成生长因子。苯那普利可促进心肌梗死IZ和BZ的血管生成，但其机制与VEGF和bFGF的表达无关。苯那普利与bFGF联合应用在一定程度上可促进VEGF和bFGF的表达，但未发现其对血管生成的影响。
