一氧化氮合酶在炎症性肠病中的表达不受皮质类固醇治疗的影响。
Expression of nitric oxide synthase in inflammatory bowel disease is not affected by corticosteroid treatment.
作者信息
Leonard N, Bishop A E, Polak J M, Talbot I C
机构信息
Department of Histopathology, St Mark's Hospital, London, UK.
出版信息
J Clin Pathol. 1998 Oct;51(10):750-3. doi: 10.1136/jcp.51.10.750.
AIM
To examine the effect of corticosteroid treatment on the expression of inducible nitric oxide synthase (iNOS) in the colon of patients with inflammatory bowel disease.
METHODS
Four groups of patients were studied: (1) ulcerative colitis treated with high dose corticosteroids (six patients, 10 blocks); (2) ulcerative colitis patients who had never received corticosteroids (10 patients, 16 blocks); (3) Crohn's disease treated with high dose corticosteroids (12 patients, 24 blocks); (4) Non-inflammatory, non-neoplastic controls (four patients, six blocks). Full thickness paraffin sections of colons removed at surgery were immunostained with an antibody raised against the C terminal end of iNOS. Sections were assessed semiquantitatively for the presence and degree of inflammation and immunoreactivity for nitric oxide synthase.
RESULTS
Cases of ulcerative colitis and Crohn's disease with active inflammation showed strong staining for nitric oxide synthase. The staining was diffuse in ulcerative colitis and patchy in Crohn's disease, in accordance with the distribution of active inflammation. Staining was seen in epithelial cells and was most intense near areas of inflammation such as crypt abscesses. Non-inflamed epithelium showed no immunoreactivity. Treatment with corticosteroids made no difference to the amount of nitric oxide synthase.
CONCLUSIONS
Expression of nitric oxide synthase is increased in both ulcerative colitis and Crohn's disease and appears to be unaffected by treatment with corticosteroids. Disease severity necessitated surgery in all the cases included in this study, regardless of whether or not the patients had received long term corticosteroid treatment. It seems therefore that a high level of iNOS expression and, presumably, production of nitric oxide characterise cases which are refractory to clinical treatment; this suggests that specific inhibition of the enzyme may be a useful therapeutic adjunct.
目的
研究皮质类固醇治疗对炎症性肠病患者结肠中诱导型一氧化氮合酶（iNOS）表达的影响。
方法
研究了四组患者：（1）接受高剂量皮质类固醇治疗的溃疡性结肠炎患者（6例，10个组织块）；（2）从未接受过皮质类固醇治疗的溃疡性结肠炎患者（10例，16个组织块）；（3）接受高剂量皮质类固醇治疗的克罗恩病患者（12例，24个组织块）；（4）非炎症性、非肿瘤性对照患者（4例，6个组织块）。手术切除的结肠全层石蜡切片用针对iNOS C末端的抗体进行免疫染色。对切片进行炎症存在和程度以及一氧化氮合酶免疫反应性的半定量评估。
结果
活动性炎症的溃疡性结肠炎和克罗恩病病例显示一氧化氮合酶染色强烈。根据活动性炎症的分布，溃疡性结肠炎中的染色呈弥漫性，克罗恩病中的染色呈斑片状。上皮细胞可见染色，在炎症区域如隐窝脓肿附近最为强烈。未发炎的上皮无免疫反应性。皮质类固醇治疗对一氧化氮合酶的量没有影响。
结论
溃疡性结肠炎和克罗恩病中一氧化氮合酶的表达均增加，且似乎不受皮质类固醇治疗的影响。本研究纳入的所有病例均因疾病严重程度而需要手术，无论患者是否接受过长期皮质类固醇治疗。因此，高水平的iNOS表达以及推测的一氧化氮产生似乎是临床治疗难治性病例的特征；这表明对该酶的特异性抑制可能是一种有用的治疗辅助手段。
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