Kanazawa S, Tsunoda T, Onuma E, Majima T, Kagiyama M, Kikuchi K
Department of Surgery, Himeji Central Hospital, Japan.
Am J Gastroenterol. 2001 Mar;96(3):822-8. doi: 10.1111/j.1572-0241.2001.03527.x.
Inflammatory bowel disease (IBD), the precise etiology of which remains unknown, is comprised of two forms of chronic intestinal inflammation; ulcerative colitis (UC) and Crohn's disease (CD). Recent evidence increasingly suggests that IBD is the result of dysfunctional immunoregulation manifested by inappropriate production of mucosal cytokines. An abnormal microcirculatory system has also been implicated in its pathogenesis. To elucidate the mechanism of ischemic change in IBD, we assesse serum concentration levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF), and plasma level of endothelin-1 (ET-1). We also investigated the expression of VEGF, b-FGF, and transforming growth factor-beta1,2,3 (TGF-beta1,2,3) in tissue by immunostaining.
Blood samples were obtained from 11 patients with UC, 11 patients with CD, and 10 patients as controls. Paraffin-embedded samples were used for an immunohistochemical study.
The concentration levels (in picograms per milliliter) were as follows: for ET-1, UC: 127+/-47.0, CD: 167.3+/-35.1, and controls (asthma: 38.5+/-23.8, p < 0.01; diverticulitis: 40.5+/-25.6, p < 0.01), for b-FGF, UC: 9.2+/-1.9, CD: 9.1+/-1.5, and controls (asthma: 5.0+/-0, p < 0.01; diverticulitis: 5.0+/-0, p < 0.01), for VEGF, UC: 659.8+/-181.0, CD: 740.0+/-182.3, and controls (asthma: 193.7+/-58.7, p < 0.01; diverticulitis: 199.6+/-59.7, p < 0.01). The levels of VEGF and b-FGF were significantly higher in active IBD than those in the controls. There was a significant positive correlation among the serum levels of VEGF and b-FGF and the plasma level of ET-1; that is, elevated VEGF, b-FGF, and ET-1 levels correlated well with each other. Immunohistochemical studies showed increased venula in the submucosa and lamina propria. Overexpression of VEGF and b-FGF in endothelial cells was revealed and TGF-beta2 and TGF-beta3 were found in inflammatory cells of active IBD, but no change was observed around the vessels in the controls.
It is suggested that the reciprocal reaction of these cytokines may contribute to angiogenesis in IBD b inducing intestinal ischemia through vasoconstriction.
炎症性肠病（IBD）的确切病因尚不清楚，它由两种慢性肠道炎症形式组成，即溃疡性结肠炎（UC）和克罗恩病（CD）。最近的证据越来越表明，IBD是黏膜细胞因子产生不当所表现出的免疫调节功能失调的结果。异常的微循环系统也被认为与其发病机制有关。为了阐明IBD中缺血变化的机制，我们评估了血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（b-FGF）的血清浓度水平以及内皮素-1（ET-1）的血浆水平。我们还通过免疫染色研究了组织中VEGF、b-FGF和转化生长因子β1、2、3（TGF-β1、2、3）的表达。
从11例UC患者、11例CD患者和10例作为对照的患者中采集血样。石蜡包埋样本用于免疫组织化学研究。
浓度水平（以皮克每毫升计）如下：ET-1方面，UC为127±47.0，CD为167.3±35.1，对照组（哮喘：38.5±23.8，p<0.01；憩室炎：40.5±25.6，p<0.01）；b-FGF方面，UC为9.2±1.9，CD为9.1±1.5，对照组（哮喘：5.0±0，p<0.01；憩室炎：5.0±0，p<0.01）；VEGF方面，UC为659.8±181.0，CD为740.0±182.3，对照组（哮喘：193.7±58.7，p<0.01；憩室炎：199.6±59.7，p<0.01）。活动期IBD中VEGF和b-FGF的水平显著高于对照组。VEGF和b-FGF的血清水平与ET-1的血浆水平之间存在显著正相关；也就是说，VEGF、b-FGF和ET-1水平的升高彼此密切相关。免疫组织化学研究显示黏膜下层和固有层的小静脉增多。内皮细胞中VEGF和b-FGF过表达，在活动期IBD的炎症细胞中发现TGF-β2和TGF-β3，但对照组血管周围未观察到变化。
提示这些细胞因子的相互反应可能通过血管收缩诱导肠道缺血，从而促进IBD中的血管生成。
