Futami K, Yamashita J, Tachibana O, Kida S, Higashi S, Ikeda K, Yamashima T
Department of Neurosurgery, Kanazawa University School of Medicine, Japan.
Stroke. 1995 Sep;26(9):1649-54. doi: 10.1161/01.str.26.9.1649.
To determine whether basic fibroblast growth factor (FGF) can induce proliferative response of endothelial cells and/or smooth muscle cells in aneurysmal lesions, we investigated the effect of the intravenous administration of basic FGF on experimental cerebral aneurysms.
Cerebral aneurysms were induced in rats by ligation of the unilateral common carotid artery, producing hypertension. Three months later, basic FGF was intravenously injected in two groups of randomly divided rats on days 1, 3, and 5 at two different doses (low dose: 2 micrograms/100 g body wt per day; high dose: 5 micrograms/100 g body wt per day). In a control group, normal saline was similarly injected. The junctions of the anterior cerebral artery (ACA) and the olfactory artery (OA) were examined with a light microscope. Aneurysmal changes were defined as the lesions with discontinuity of the internal elastic lamina in more than half of the outward dilated wall. Depending on whether the smooth muscle cell layer was present in the whole wall, the lesions were divided into two stages: early aneurysmal lesion (whole area) and saccular aneurysm (not totally preserved).
The control and the low-dose groups presented no obvious intimal thickening in the intact ACA-OA junctions of both nonligated and ligated sides as well as in the aneurysmal changes. In contrast, in the high-dose group, various degrees of intimal thickening in the wall were detected in 7 of 15 early aneurysmal lesions (P = .019, Fisher's exact test). Immunohistochemistry showed the proliferated cells to be smooth muscle cells.
These results demonstrate that exogenous basic FGF induces the proliferative response of smooth muscle cells in aneurysmal lesions in rats.
为了确定碱性成纤维细胞生长因子（FGF）是否能诱导动脉瘤病变中内皮细胞和/或平滑肌细胞的增殖反应，我们研究了静脉注射碱性FGF对实验性脑动脉瘤的影响。
通过结扎单侧颈总动脉使大鼠产生高血压，从而诱发脑动脉瘤。三个月后，将两组随机分组的大鼠在第1、3和5天分别以两种不同剂量静脉注射碱性FGF（低剂量：2微克/100克体重/天；高剂量：5微克/100克体重/天）。在对照组中，同样注射生理盐水。用光学显微镜检查大脑前动脉（ACA）和嗅动脉（OA）的连接处。动脉瘤变化定义为向外扩张壁的一半以上出现内弹性膜连续性中断的病变。根据整个壁中是否存在平滑肌细胞层，将病变分为两个阶段：早期动脉瘤病变（整个区域）和囊状动脉瘤（未完全保留）。
对照组和低剂量组在未结扎侧和结扎侧完整的ACA - OA连接处以及动脉瘤变化中均未出现明显的内膜增厚。相比之下，在高剂量组中，15个早期动脉瘤病变中有7个检测到壁内不同程度的内膜增厚（P = .019，Fisher精确检验）。免疫组织化学显示增殖细胞为平滑肌细胞。
这些结果表明，外源性碱性FGF可诱导大鼠动脉瘤病变中平滑肌细胞的增殖反应。
