Yamamura Mitsuhiro, Miyamoto Yuji, Mitsuno Masataka, Tanaka Hiroe, Kobayashi Yasuhiko, Ryomoto Masaaki
Department of Cardiovascular Surgery, Hyogo College of Medicine, Hyogo, Japan.
Int J Angiol. 2007 Winter;16(4):143-5. doi: 10.1055/s-0031-1278269.
Postoperative intimal hyperplasia, the most common cause of vein graft occlusion, is initiated by endothelial injury. In the present study, the mechanism by which the free radical scavenger edaravone (Radicut, Mitsubishi Tanabe Pharma Co, Japan) protects against endothelial injury in postoperative intimal hyperplasia was investigated.
In 18 male Lewis rats, a right epigastric vein graft was interposed into the common femoral artery. Nine rats received a pre-operative intraperitoneal administration of edaravone (3.0 mg/kg, edaravone group) and the other nine rats received an equal volume of saline (saline group). After 1 h, five vein grafts from each group were treated with Verhoeff-van Gieson elastica stain and subjected to a histological examination. The other four vein grafts from each group were examined with an S-800 Hitachi scanning electron microscope (SEM) (Hitachi High-Technologies Co, Japan) at ×1000 magnification, as were three unoperated right epigastric veins (unoperated vein group). The endothelial areas of the vein grafts were measured using computerized planimetry of the SEM images (ImageJ version 1.37, National Institutes of Health, USA). The mean endothelial areas (%) were compared between the two groups.
Verhoeff-van Gieson elastica stain revealed no significant differences between the two groups. SEM showed that endothelial cells in the unoperated epigastric vein had a cobblestone-like appearance. In the saline group, the endothelial cells were comb-shaped and had adherent monocytes. In the edaravone group, however, the cobblestone-like appearance of endothelial cells was well preserved, with little monocyte adhesion. Moreover, the mean (± standard error of the mean) endothelial area was significantly higher in vein grafts from the edaravone group than in those from the saline group (74±1.8% versus 56±4.3%, P<0.05), and was similar to those in the unoperated epigastric veins (72±1.9%).
These findings show that endothelial injury is present soon after placement of the interposition graft. The authors believe that edaravone suppresses postoperative intimal hyperplasia by alleviating endothelial injury.
术后内膜增生是静脉移植物闭塞最常见的原因，由内皮损伤引发。在本研究中，探讨了自由基清除剂依达拉奉（Radicut，日本三菱田边制药公司）预防术后内膜增生中内皮损伤的机制。
选取18只雄性Lewis大鼠，将右腹壁静脉移植物植入股总动脉。9只大鼠术前腹腔注射依达拉奉（3.0mg/kg，依达拉奉组），另外9只大鼠注射等量生理盐水（生理盐水组）。1小时后，每组5个静脉移植物用Verhoeff-van Gieson弹性组织染色并进行组织学检查。每组另外4个静脉移植物用日立S-800扫描电子显微镜（SEM）（日本日立高新技术公司）以1000倍放大倍数检查，3个未手术的右腹壁静脉（未手术静脉组）也进行同样检查。使用SEM图像的计算机图像分析（美国国立卫生研究院ImageJ 1.37版）测量静脉移植物的内皮面积。比较两组的平均内皮面积（%）。
Verhoeff-van Gieson弹性组织染色显示两组间无显著差异。SEM显示，未手术的腹壁静脉内皮细胞呈鹅卵石样外观。生理盐水组中，内皮细胞呈梳状且有黏附的单核细胞。然而，在依达拉奉组，内皮细胞的鹅卵石样外观保存良好，单核细胞黏附很少。此外，依达拉奉组静脉移植物的平均（±平均标准误）内皮面积显著高于生理盐水组（74±1.8%对56±4.3%，P<0.05），且与未手术的腹壁静脉相似（72±1.9%）。
这些发现表明，植入间置移植物后不久即存在内皮损伤。作者认为依达拉奉通过减轻内皮损伤抑制术后内膜增生。
