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短期局部应用皮质类固醇治疗对远端炎症性肠病患者黏膜酶系统的影响。

Effect of short-term topical corticosteroid treatment on mucosal enzyme systems in patients with distal inflammatory bowel disease.

作者信息

Scheurlen C, Allgayer H, Hardt M, Kruis W

机构信息

Department of General Internal Medicine, University of Bonn, Germany.

出版信息

Hepatogastroenterology. 1998 Sep-Oct;45(23):1539-45.

PMID:9840102
Abstract

BACKGROUND/AIMS: Glucocorticoids, even when administered topically, have a known early benefit on diarrheal symptoms in inflammatory bowel diseases which may not be explained exclusively by their anti-inflammatory effect. Therefore, we evaluated a possible early effect of topically administered glucocorticosteroids on the mucosal function of patients with distal inflammatory bowel disease in a prospective, controlled study, which was blinded for histological evaluation.

METHODOLOGY

Eleven patients with distal ulcerative colitis or Crohn's disease, and 8 patients without intestinal inflammation were studied. A sigmoidoscopy with biopsy sampling (8-10) was performed before and 3 days after rectal administration of a hydrocortisone acetate foam preparation (100 mg b.i.d.). Prior to and after topical steroid treatment, basolateral (Na++K+)-ATPase activity (coupled optical assay), specific 3H ouabain binding (rapid filtration method), 5'-nucleotidase (microdetection method of phosphorus), and mucosal DNA levels (diphenylamine reaction) were determined from biopsy homogenates. Morphological and clinical characteristics were assessed according to established scores.

RESULTS

Short-term topical GCS treatment significantly (p<0.05) stimulated (Na++K+)-ATPase activity (103%) as well as the number of active (Na++K+)-ATPase molecules (190%). In the healthy mucosa, only (Na++K+)-ATPase activity was stimulated (124%, p<0.05; specific 3H ouabain binding: 33%; p=0.09). As an unspecific GCS effect, apical 5'-nucleotidase was also stimulated (p<0.05; IBD: 50%; controls: 200%). As assessed by endoscopic and histological scores, as well as by mucosal DNA levels, morphological signs of intestinal inflammation remained unchanged during the study, whereas the daily stool frequency decreased significantly (p<0.05).

CONCLUSIONS

In patients with distal inflammatory bowel disease, short-term treatment with topical GCS leads to a quick recovery from diarrheal symptoms, due to the early improvement of mucosal function prior to the occurrence of the well-known anti-inflammatory GCS effect.

摘要

背景/目的:糖皮质激素即使局部给药,对炎症性肠病的腹泻症状也有早期益处,这可能无法完全用其抗炎作用来解释。因此,我们在一项前瞻性对照研究中评估了局部应用糖皮质激素对远端炎症性肠病患者黏膜功能的可能早期影响,该研究对组织学评估采用盲法。

方法

研究了11例远端溃疡性结肠炎或克罗恩病患者以及8例无肠道炎症的患者。在直肠给予醋酸氢化可的松泡沫制剂(100mg,每日两次)前及给药3天后进行乙状结肠镜检查并取活检样本(8 - 10块)。在局部类固醇治疗前后,从活检匀浆中测定基底外侧(Na⁺⁺K⁺)-ATP酶活性(偶联光学测定法)、特异性³H哇巴因结合(快速过滤法)、5'-核苷酸酶(磷的微量检测法)以及黏膜DNA水平(二苯胺反应)。根据既定评分评估形态学和临床特征。

结果

短期局部糖皮质激素治疗显著(p<0.05)刺激了(Na⁺⁺K⁺)-ATP酶活性(103%)以及活性(Na⁺⁺K⁺)-ATP酶分子数量(190%)。在健康黏膜中,仅(Na⁺⁺K⁺)-ATP酶活性受到刺激(124%,p<0.05;特异性³H哇巴因结合:33%;p = 0.09)。作为糖皮质激素的非特异性作用,顶端5'-核苷酸酶也受到刺激(p<0.05;炎症性肠病:50%;对照组:200%)。通过内镜和组织学评分以及黏膜DNA水平评估,在研究期间肠道炎症形态学征象未改变,但每日大便频率显著降低(p<0.05)。

结论

对于远端炎症性肠病患者,局部糖皮质激素短期治疗可使腹泻症状迅速缓解,这是由于在糖皮质激素众所周知的抗炎作用出现之前黏膜功能就得到了早期改善。

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