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

肠道三叶因子（ITF）在胃肠道创面愈合过程中起着重要作用。内镜下粘膜切除术（EMR）是治疗早期胃癌的常用方法。手术后，患者需要限制饮食或药物，如抗酸或粘膜保护药物，以保护脱落区域或促进人工溃疡愈合。我们研究了ITF是否可以作为内镜下粘膜切除术（EMR）引起的人工溃疡的治疗方法。在EMR大鼠胃模型中测试了ITF的作用。大鼠胃中ITF基因表达水平几乎检测不到。内源性ITF表达在EMR后第1天升高，第3天达到最高水平，RT-PCR检测。虽然外源性ITF喷在溃疡表面只持续到术后第1天，但从宏观和微观上看，ITF显著加速了粘膜愈合。ITF治疗后溃疡愈合的特征性表现为炎症程度或程度减轻，溃疡附近上皮细胞坏死减少，溃疡表面再上皮化增强，纤维化减少。总的来说，ITF以类似于胃溃疡自然愈合过程的方式加速了人工溃疡的愈合。从ITF作为临床治疗药物的安全性角度出发，在内源性TFF3阳性和阴性胃癌细胞株中评估TFF3对增殖反应的刺激作用。ITF对所有被测试的细胞系没有任何刺激作用，这表明ITF可能是EMR引起的溃疡的有效治疗方法，用于癌症的治疗。总之，我们目前的研究证明了修复的临床重要性，这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。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