Investigation of the possibility of Trefoil Factor Family as a therapeutics for post-EMR (endoscopic mucosal resection) gastric ulcer

内源性三叶因子(ITF)在胃肠道创面愈合过程中起重要作用。内窥镜黏膜切除术(EMR)是治疗早期胃癌的一种常用方法。手术后，患者需要有限的饮食或药物，如抗酸或粘膜保护药物，以保护裸露区域或促进人工溃疡的愈合。我们研究了ITF是否可以作为治疗内窥镜下黏膜切除术(EMR)所致的人工溃疡的药物。在大鼠胃EMR模型上验证了ITF的作用。大鼠胃组织中ITF基因表达水平几乎检测不到。逆转录-聚合酶链式反应检测到内源性ITF在EMR后1d表达增强，3d达最高水平。虽然外源性itf喷洒在溃疡表面只持续到术后第1天，但itf在宏观上显著促进了粘膜的愈合，正如我们所说的…更多的是微观上的。ITF治疗后溃疡愈合的特点是炎症程度减轻，溃疡周围上皮细胞坏死减少，溃疡表面再上皮化增强，纤维化减轻。总体而言，ITF以类似于胃溃疡自然愈合的方式促进了人工溃疡的愈合。从ITF作为临床治疗药物的安全性角度，评价了TFF3对内源性TFF3阳性和阴性胃癌细胞系增殖反应的刺激作用。ITF对所有受试细胞株均无刺激作用，提示ITF可能是治疗EMR所致肿瘤溃疡的有效药物。综上所述，我们目前的研究证明了修复的临床重要性，修复是上皮伤口愈合的初始阶段，并由外源性ITF促进。ITF可能是一种治疗EMR后胃溃疡的新方法。较少

Intesitnal trefoil factor (ITF) plays an important role in the process of wound healing of gastrointestinal tract. Endoscopic mucosal resection (EMR) is a prevailing procedure for the treatment of early gastric cancers. Following the procedure, patients need limited diet or medication such as anti-acid or muco-protective drugs for the protection of denuded area or facilitating the healing of the artificial ulceration. We have investigated if ITF could be useful as the therapeutics for the artificial ulceration caused by endoscopic mucosal resection (EMR). The effect of ITF was tested in a rat stomach model of EMR. The level of ITF gene expression in rat stomach was almost undetectable. Increased endogenous expression of ITF was observed on 1 day after EMR and maximum level was observed on day 3, which was examined by RT-PCR. Although exogenous ITF sprayed upon ulcer surface stayed only up to postoperative day 1, ITF significantly accelerated the mucosal healing in macroscopically as we … More ll as microscopically. The characteristic appearances of ulcer healing treated by ITF were attenuated the extent or the degree of inflammation, reduced necrosis of epithelial cells adjacent to the ulcer, enhanced re-epithelization of ulcer surface and decreased fibrosis. In aggregate, ITF accelerated the healing of artificial ulceration in a manner similar to natural healing process of gastric ulcer. In the view point of safety of ITF as clinical therapeutics, the stimulatory effect of TFF3 on proliferative response was evaluated in either endogenous TFF3 positive or negative gastric cancer cell lines. ITF did not have any stimulatory effect on all cell lines tested, which suggesting that ITF might be a effective therapeutics for the ulcerations caused by EMR for the management of carcinomas. In summary, our present study demonstrated the clinical importance of restitution, which is an initial phase of epithelial wound healing and promoted by exogenous administration of ITF. ITF might be a new therapeutics against post-EMR gastric ulceration. Less