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口服三叶因子2(TFF2)的代谢以及口服和胃肠外给予TFF2对大鼠胃溃疡和十二指肠溃疡愈合的影响。

Metabolism of oral trefoil factor 2 (TFF2) and the effect of oral and parenteral TFF2 on gastric and duodenal ulcer healing in the rat.

作者信息

Poulsen S S, Thulesen J, Christensen L, Nexo E, Thim L

机构信息

Department of Medical Anatomy B, University of Copenhagen, Copenhagen, Denmark.

出版信息

Gut. 1999 Oct;45(4):516-22. doi: 10.1136/gut.45.4.516.

DOI:10.1136/gut.45.4.516
PMID:10486358
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1727673/
Abstract

BACKGROUND

Trefoil factors (TFFs) are peptides produced by mucus-secreting cells in the gastrointestinal tract. A functional association between these peptides and mucus, leading to stabilisation of the viscoelastic gel overlying the epithelia, has been suggested. Both oral and parenteral administration of the peptides increase the resistance of the gastric mucosa.

AIM

To study the effect in rats of oral and parenteral porcine trefoil factor 2 (pTFF2) on the healing of gastric and duodenal ulcerations and to clarify the distribution and metabolism of orally administered pTFF2 in the gastrointestinal tract.

METHODS

Gastric ulcers were induced in female Sprague-Dawley rats by indomethacin and duodenal ulcers by mercaptamine. The rats were treated for up to seven days with oral or subcutaneous pTFF2. Ulcer size after treatment was assessed by stereomicroscopy after whole mount staining with periodic acid-Schiff stain. (125)I-labelled pTFF2 was given orally to rats, and tissues were investigated by gamma counting of samples and by autoradiography of paraffin embedded sections.

RESULTS

pTFF2 accelerated gastric ulcer healing after both oral and subcutaneous administration. Duodenal ulcers were aggravated by both treatments. After oral administration of (125)I-pTFF2, intact peptide was recovered from the superficial part of the mucus layer in the stomach; it passed through the small intestine but was degraded in the caecum. Only a minor part of the labelled pTFF2 entered the colon and was excreted in the faeces. Most of the label was excreted in the urine.

CONCLUSIONS

Oral as well as parenteral pTFF2 accelerates the healing of gastric ulceration and aggravates duodenal ulcers. Oral pTFF2 binds to the mucus layer of the stomach and the small intestine but does not reach the colonic mucosa.

摘要

背景

三叶因子(TFFs)是胃肠道黏液分泌细胞产生的肽类。有人提出这些肽与黏液之间存在功能关联,可使覆盖上皮的黏弹性凝胶稳定。肽类的口服和胃肠外给药均可增加胃黏膜的抵抗力。

目的

研究口服和胃肠外给予猪三叶因子2(pTFF2)对大鼠胃溃疡和十二指肠溃疡愈合的影响,并阐明口服pTFF2在胃肠道中的分布和代谢。

方法

用吲哚美辛诱导雌性斯普拉格-道利大鼠产生胃溃疡,用巯基乙胺诱导产生十二指肠溃疡。用口服或皮下注射pTFF2对大鼠进行长达7天的治疗。治疗后,用高碘酸-希夫染色进行整装染色,通过体视显微镜评估溃疡大小。给大鼠口服碘(125)标记的pTFF2,通过对样品进行γ计数和对石蜡包埋切片进行放射自显影来研究组织。

结果

口服和皮下注射pTFF2后均可加速胃溃疡愈合。两种治疗均使十二指肠溃疡加重。口服碘(125)标记的pTFF2后,在胃黏液层表层可回收完整的肽;它通过小肠,但在盲肠中降解。只有一小部分标记的pTFF2进入结肠并随粪便排出。大部分标记物经尿液排出。

结论

口服和胃肠外给予pTFF2均可加速胃溃疡愈合并加重十二指肠溃疡。口服pTFF2与胃和小肠的黏液层结合,但未到达结肠黏膜。

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本文引用的文献

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Distribution and metabolism of intravenously administered trefoil factor 2/porcine spasmolytic polypeptide in the rat.静脉注射三叶因子2/猪解痉多肽在大鼠体内的分布与代谢
Gut. 1998 Aug;43(2):240-7. doi: 10.1136/gut.43.2.240.
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Trefoil peptides: from structure to function.三叶肽:从结构到功能
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Characterization of a putative receptor for intestinal trefoil factor in rat small intestine: identification by in situ binding and ligand blotting.大鼠小肠中肠三叶因子假定受体的特性:通过原位结合和配体印迹法鉴定
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Pancreatic spasmolytic polypeptide protects the gastric mucosa but does not inhibit acid secretion or motility.胰腺解痉多肽可保护胃黏膜,但不抑制胃酸分泌或胃动力。
Am J Physiol. 1997 Jul;273(1 Pt 1):G112-7. doi: 10.1152/ajpgi.1997.273.1.G112.
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Rolling in the clover: trefoil factor family (TFF)-domain peptides, cell migration and cancer.在三叶草中打滚:三叶因子家族(TFF)结构域肽、细胞迁移与癌症
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Science. 1996 Oct 11;274(5285):262-5. doi: 10.1126/science.274.5285.262.
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The trefoil peptide family.三叶肽家族。
Annu Rev Physiol. 1996;58:253-73. doi: 10.1146/annurev.ph.58.030196.001345.
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Transgenic mice that overexpress the human trefoil peptide pS2 have an increased resistance to intestinal damage.过度表达人三叶肽pS2的转基因小鼠对肠道损伤的抵抗力增强。
Proc Natl Acad Sci U S A. 1996 Mar 5;93(5):2137-42. doi: 10.1073/pnas.93.5.2137.
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Oral trefoil peptides protect against ethanol- and indomethacin-induced gastric injury in rats.口服三叶肽可预防大鼠乙醇和吲哚美辛诱导的胃损伤。
Gastroenterology. 1996 Feb;110(2):489-97. doi: 10.1053/gast.1996.v110.pm8566596.