Harada Masakazu, Takenaka Hiroaki, Ikenaga Sigeru, Zhang Hua, Zempo Nobuya, Esato Kensuke, Nagano Tomokazu, Taiji Mutsuo, Noguchi Hiroshi
First Department of Surgery, Yamaguchi University School of Medicine, Ube, Japan.
J Vasc Surg. 2002 Apr;35(4):786-91. doi: 10.1067/mva.2002.119747.
The major cause of vascular prosthesis failure is anastomotic intimal hyperplasia caused by the proliferation and migration of smooth muscle cells. Hepatocyte growth factor (HGF) is an endothelium-specific growth factor that exerts a mitogenic action on endothelial cells. This study was designed to examine the effect of HGF on the suppression of intimal hyperplasia after small-caliber expanded polytetrafluoroethylene (ePTFE) grafting.
An ePTFE graft, 2 mm in diameter and 30 mm in length, was implanted in the left common carotid arteries of Japanese white rabbits, after which the animals were fed with a 1.0% cholesterol diet. HGF was infused intravenously immediately and then every day for 7 days at doses of 0.3 mg/body (the 0.3-mg HGF group; n = 20) or 1.0 mg/body (the 1.0-mg HGF group; n = 17). A control group (n = 20) underwent infusion with saline solution. The rabbits were killed on postoperative days (PODs) 1, 2, 3, 5, 7, and 28.
The patency rates on POD 28 were 33%, 55%, and 100% in the control, the 0.3-mg HGF, and the 1.0-mg HGF groups, respectively, with a significant difference between the control and the 1.0-mg HGF group (P <.05). Endothelial-like cells were seen on the intraluminal surface of the graft only near the anastomotic site on POD 5 in the 1.0-mg HGF group. Intimal thickness at the distal anastomosis was 284 +/- 140 microm, 106 +/- 18 microm, and 67 +/- 10 microm in the control, the 0.3-mg HGF, and the 1.0-mg HGF groups, respectively, with a significant difference between the control and both HGF groups (P <.05). The number of anti-embryonic smooth muscle antibody positive cells at the distal anastomosis was 28.6 +/- 0.8, 3.8 +/- 2.8, and 3.9 +/- 0.9 in the control, the 0.3-mg HGF, and the 1.0-mg HGF groups, respectively, with a significant difference between the control and both HGF groups (P <.01).
HGF might suppress intimal thickness at the anastomotic site and improve the patency rate via rapid reendothelialization by POD 28 in a rabbit carotid ePTFE grafting model.
血管假体失败的主要原因是平滑肌细胞增殖和迁移导致的吻合口内膜增生。肝细胞生长因子（HGF）是一种内皮特异性生长因子，对内皮细胞具有促有丝分裂作用。本研究旨在探讨HGF对小口径膨体聚四氟乙烯（ePTFE）移植后内膜增生的抑制作用。
将直径2mm、长度30mm的ePTFE移植物植入日本白兔的左颈总动脉，术后给予1.0%胆固醇饮食。立即静脉注射HGF，然后每天注射，共7天，剂量分别为0.3mg/只（0.3mg HGF组；n = 20）或1.0mg/只（1.0mg HGF组；n = 17）。对照组（n = 20）输注生理盐水。在术后第1、2、3、5、7和28天处死兔子。
术后28天，对照组、0.3mg HGF组和1.0mg HGF组的通畅率分别为33%、55%和100%，对照组与1.0mg HGF组之间有显著差异（P <.05）。在1.0mg HGF组中，术后第5天仅在吻合口附近的移植物管腔内表面可见内皮样细胞。对照组、0.3mg HGF组和1.0mg HGF组远端吻合口处的内膜厚度分别为284±140μm、106±18μm和67±10μm，对照组与两个HGF组之间有显著差异（P <.05）。对照组、0.3mg HGF组和1.0mg HGF组远端吻合口处抗胚胎平滑肌抗体阳性细胞数分别为28.6±0.8、3.8±2.8和3.9±0.9，对照组与两个HGF组之间有显著差异（P <.01）。
在兔颈动脉ePTFE移植模型中，HGF可能通过在术后28天快速重新内皮化来抑制吻合口处的内膜厚度并提高通畅率。
