克罗恩病性结肠炎中一氧化氮合酶及人类白细胞抗原DR表达与闭塞性动脉炎的关系

Yokoyama K, Mitomi H, Kobayashi K, Katsumata T, Saigenji K, Okayasu I

Department of Internal Medicine, School of Medicine, Kitasato University East Hospital, 2-1-1 Asamizo-dai, Sagamihara, Kanagawa 228-8520, Japan.

Hepatogastroenterology. 2001 Mar-Apr;48(38):401-7.

BACKGROUND/AIMS: To cast light on whether inflammatory vascular injury is a possible pathogenic mechanism in Crohn's disease, the histological characteristics of vascular lesions were investigated.

METHODOLOGY

Affected vessels in surgically resected colons from 23 patients with Crohn's disease, 20 with ulcerative colitis, 7 with ischemic colitis, and 9 normal controls were analyzed by Victoria blue and hematoxylin and eosin staining as well as immunohistochemistry for HLA-DR, nitric oxid synthase, vascular endothelial growth factor and E-cadherin.

RESULTS

Inflammatory-cell infiltrates affecting arteries, accompanied by obliterative intimal thickening, were more frequent in Crohn's disease cases than in the other groups (P < 0.05-0.0001). Crohn's disease activity was positively correlated with the degree of obliterative arteritis. Granulomatous vasculitis was found exclusively in Crohn's disease (10 cases; 43.5%). In addition, focally enhanced endothelial staining of HLA-DR, with expression in granulomas adjacent to vessels was occasionally observed. In the endothelium of affected vessels, strong expression of HLA-DR was more prevalent in Crohn's disease and/or ulcerative colitis as compared with the ischemic colitis and controls (P < 0.05-0.01). In the involved arteries, enhanced endothelial nitric oxide synthase expression was most common in Crohn's disease among the groups (P < 0.05). A few cases of Crohn's disease, ulcerative colitis and ischemic colitis were positive for inducible nitric oxide synthase, vascular endothelial growth factor or E-cadherin in the vessel walls.

CONCLUSIONS

The presence of characteristic obliterative arteritis and granulomatous vasculitis, a possible cause of ischemic injury, supports, in part, a vascular hypothesis for the pathogenesis of Crohn's disease. Enhanced expression of endothelial nitric oxide synthase and HLA-DR possibly reflects compensatory endothelium-mediated vasodilation and amplification of the immune response, respectively.

背景/目的：为了阐明炎症性血管损伤是否为克罗恩病可能的致病机制，对血管病变的组织学特征进行了研究。

方法

对23例克罗恩病患者、20例溃疡性结肠炎患者、7例缺血性结肠炎患者手术切除的结肠以及9例正常对照的受累血管进行维多利亚蓝、苏木精和伊红染色，以及HLA-DR、一氧化氮合酶、血管内皮生长因子和E-钙黏蛋白的免疫组织化学分析。

结果

与其他组相比，克罗恩病患者中影响动脉的炎性细胞浸润伴闭塞性内膜增厚更为常见（P<0.05-0.0001）。克罗恩病活动度与闭塞性动脉炎程度呈正相关。肉芽肿性血管炎仅在克罗恩病中发现（10例；43.5%）。此外，偶尔观察到HLA-DR在内皮细胞中的局灶性增强染色，并在血管周围的肉芽肿中表达。与缺血性结肠炎和对照组相比，HLA-DR在克罗恩病和/或溃疡性结肠炎受累血管内皮中的强表达更为普遍（P<0.05-0.01）。在受累动脉中，内皮型一氧化氮合酶表达增强在各组中以克罗恩病最为常见（P<0.05）。少数克罗恩病、溃疡性结肠炎和缺血性结肠炎病例的血管壁中诱导型一氧化氮合酶、血管内皮生长因子或E-钙黏蛋白呈阳性。