Anti-inflammatory effect of diosmectite in hapten-induced colitis in the rat
Anti-inflammatory effect of diosmectite in hapten-induced colitis in the rat
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DOI：
10.1038/sj.bjp.0705710
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发表时间：
2004-03-01
影响因子：
7.3
通讯作者：
Zarzuelo, A
中科院分区：
文献类型：
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作者：
González, R;de Medina, FS;Zarzuelo, A
1蒙脱石是一种天然硅酸盐，可有效治疗感染性腹泻。它的抗消化道炎特性包括吸附毒素和细菌以及改变胃肠道粘液的流变学特性。因此，本研究的目的是测试蒙脱石的肠道抗炎活性。2蒙脱石（500 mg/kg/天，p.o.）作为治疗后给药于患有慢性三硝基苯磺酸结肠炎的大鼠。在结肠炎诱导后1周和2周，通过肉眼、组织学和生化检查检查结肠状态。3蒙脱石后处理导致形态学体征改善（肠重量、肉眼可见损伤、坏死面积、组织学）和生化标志物（髓过氧化物酶活性，谷胱甘肽水平，MUC 2表达，诱导型一氧化氮合酶和白细胞介素-1 β（IL-1 β）和白三烯B-4合成），以及降低腹泻的严重程度。粘土的效果与柳氮磺胺吡啶相当（50 mg kg（-1）天（-1））。4蒙脱石在体外表现出剂量依赖性的蛋白质吸附能力，以及对脂多糖（LPS）刺激的HT 29细胞的基底外侧IL-8分泌的剂量依赖性抑制作用。5蒙脱石对LPS刺激的THP产生的IL-1 β具有剂量依赖性抑制作用。6蒙脱石对MUC 2的影响是转录后的，因为mRNA水平不受影响。然而，蒙脱石能够上调HT 29-MTX细胞中的MUC 2 mRNA水平。7蒙脱石具有抗炎活性，可作为后治疗给药。可能的机制包括管腔抗原的吸附、结肠粘蛋白水平的增加以及粘膜细胞产生细胞因子的可能的直接调节作用。
1 Diosmectite is a natural silicate effectively used in the treatment of infectious diarrhoea. Its antidiarrhoeal properties involve adsorption of toxins and bacteria and modifications of the rheological characteristics of gastrointestinal mucus. Hence, the aim of this study was to test the intestinal anti-inflammatory activity of diosmectite.2 Diosmectite (500 mg kg(-1) day(-1), p.o.) was administered as a post-treatment to rats with chronic trinitrobenzene sulphonic acid colitis. Colonic status was checked 1 and 2 weeks after colitis induction by macroscopic, histological and biochemical examination.3 Diosmectite post-treatment resulted in amelioration of the morphological signs (intestinal weight, macroscopic damage, necrosed area, histology) and biochemical markers (myeloperoxidase activity, glutathione levels, MUC2 expression, inducible nitric oxide synthase and interleukin-1beta (IL-1beta) and leukotriene B-4 synthesis), as well as in the reduction of the severity of diarrhoea. The effect of the clay was comparable to that of sulphasalazine (50 mg kg(-1) day(-1)).4 Diosmectite exhibited a dose-dependent capacity to adsorb proteins in vitro as well as a dose-dependent inhibitory effect on the basolateral secretion of IL-8 by lipopolysaccharide (LPS)-stimulated HT29 cells.5 Diosmectite had a dose-dependent inhibitory effect on IL-1beta production by LPS-stimulated THP-1 cells.6 The effect of diosmectite on MUC2 was post-transcriptional, since mRNA levels were unaffected. However, diosmectite is able to upregulate MUC2 mRNA levels in HT29-MTX cells.7 Diosmectite has anti-inflammatory activity administered as a post-treatment. Possible mechanisms include adsorption of luminal antigens, increase of colonic mucin levels and possibly a direct modulatory action of cytokine production by mucosal cells.