Griga T, Voigt E, Gretzer B, Brasch F, May B
Department of Gastroenterology, University of Bochum, Germany.
Hepatogastroenterology. 1999 Mar-Apr;46(26):920-3.
BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is a heparin-binding glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells. Recent studies have shown significantly increased VEGF serum levels in patients with active Crohn's disease and ulcerative colitis. The origin of the circulating VEGF is not yet completely described. The present investigation examines the VEGF production of colonic mucosa in consideration of mucosal disease activity in patients with inflammatory bowel disease.
Fifteen patients with inflammatory bowel disease were studied, 9 patients with Crohn's disease and 6 patients with ulcerative colitis. Biopsies were taken from endoscopically inflamed and non-inflamed colonic mucosa. Therefore, an analysis of the spontaneous VEGF production of cultured biopsies without stimulus and of the histological grade of inflammation scored on a scale of 0-3 (normal mucosa--severe chronic colitis) were performed. Eight patients with irritable bowel syndrome served as controls. VEGF levels in the supernatant of cultured mucosal biopsies were measured using an enzyme linked immunosorbent assay.
VEGF production is expressed as pg/mg wet weight of the biopsies. Inflamed mucosa of patients with active ulcerative colitis (16.27 +/- 10.39, p = 0.003, n = 6) and active Crohn's disease (9.88 +/- 5.98, p < 0.012, n = 9) showed a significantly higher spontaneous production of VEGF by colonic mucosa than normal mucosa of controls (3.16 +/- 1.63, n = 8). In addition, there was an increased unstimulated VEGF production by cultured inflamed mucosa of patients with Crohn's disease compared with non-inflamed mucosa (3.88 +/- 3.66, p < 0.015, n = 9). In both Crohn's disease and ulcerative colitis, there was no significant difference between VEGF production by non-inflamed mucosa and normal mucosa of controls.
The present study identifies the intestinal mucosa as one of the origins of the elevated VEGF serum levels in patients with active inflammatory bowel disease and verifies the findings of recent studies about the importance of VEGF in Crohn's disease and ulcerative colitis.
背景/目的:血管内皮生长因子(VEGF)是一种肝素结合糖蛋白,对内皮细胞具有强大的血管生成、促有丝分裂和增强血管通透性的活性。最近的研究表明,活动性克罗恩病和溃疡性结肠炎患者的VEGF血清水平显著升高。循环VEGF的来源尚未完全阐明。本研究考虑炎症性肠病患者的黏膜疾病活动情况,检测结肠黏膜中VEGF的产生。
研究了15例炎症性肠病患者,其中9例克罗恩病患者,6例溃疡性结肠炎患者。从内镜检查显示有炎症和无炎症的结肠黏膜取活检组织。因此,对未受刺激的培养活检组织的自发VEGF产生情况以及根据0 - 3级(正常黏膜 - 重度慢性结肠炎)评分的炎症组织学分级进行了分析。8例肠易激综合征患者作为对照。使用酶联免疫吸附测定法测量培养的黏膜活检组织上清液中的VEGF水平。
VEGF产生量以活检组织湿重的pg/mg表示。活动性溃疡性结肠炎患者(16.27±10.39,p = 0.003,n = 6)和活动性克罗恩病患者(9.88±5.98,p < 0.012 = 9)的炎症黏膜中结肠黏膜自发产生的VEGF明显高于对照的正常黏膜(3.16±1.63,n = 8)。此外,与非炎症黏膜相比,克罗恩病患者培养的炎症黏膜中未受刺激的VEGF产生增加(3.88±3.66,p < 0.015,n = 9)。在克罗恩病和溃疡性结肠炎中,非炎症黏膜与对照正常黏膜的VEGF产生之间均无显著差异。
本研究确定肠黏膜是活动性炎症性肠病患者VEGF血清水平升高的来源之一,并证实了最近关于VEGF在克罗恩病和溃疡性结肠炎中重要性的研究结果。