小肠三叶因子保护胃黏膜促进溃疡愈合的实验研究

目的:研究基因重组人小肠三叶因子(recombinant human intestinal trefoil factor , rhITF)促进慢性胃溃疡的愈合、保护胃黏膜抵抗多种损伤的作用及其机制.方法:(1) 急性损伤方法:用乙醇,阿司匹林,应激和幽门结扎诱发胃黏膜损伤,用Guth法测定损伤指数.(2)慢性溃疡产生法:用50%(质量分数)乙酸接触胃体部桨膜面.损伤后第2天开始经口灌 rhITF 11 d,第12天麻醉下测定胃黏膜面血流量(GMBF),取胃液测定胃酸排除量,检查溃疡指数、胃黏膜氨基己糖和一氧化氮浓度,检测溃疡底部一氧化氮合酶iNOS mRNA的表达.结果: rhITF有保护胃黏膜抗急性损伤的作用,在应激诱发的损伤中,胃黏膜糖蛋白含量增加.rhITF促进慢性胃溃疡的愈合,治疗组和对照组比较,溃疡指数和胃酸排除量明显减少(P<0.05),GMBF、Hex和NO含量及iNOS mRNA表达增加(P<0.05).结论:rhITF 保护胃黏膜可能和胃黏膜黏液糖蛋白增加有关.rhITF促进慢性胃溃疡愈合,其机制可能增加Hex含量和GMBF,抑制胃酸,刺激 iNOS的表达.

Effect of recombinant human trefoil factor on protection of gastric mucosa and healing of chronic gastric ulcer in rats

Objective: To study the effect of recombinant human intestinal trefoil factor ( rhITF) on the healing of rat chronic gastric ulcer , protect gastric mucosal and mechanisms are involved. Methods: (1) Acute gastric mucosal injury was induced by ethanol, stress, aspirin and pylorusl ligation. The injury index ,MDA, GMBL,hexosamine (Hex) and acid output were measure. (2) Chronic gastric ulcer was induced in rats by application of 50% glacial acetic acid to the serosa of the glandular stomach. After injury, rats received by rhITF or vehicle orally twice daily for 11 days. On day 12, gastric mucosal blood flow(GMBF)was measured under ether anesthesia. Then the pylorus was ligated for 3 hours and each stomach removed. The gastric acid output, ulcer index, Hex and nitric oxide(NO) content in gastric mucosa, as well as iNOSmRNA in the ulcer bed were determined. Results: (1) rhITF protected gastric mucosa from the acute lesion, and increased Hex content in gastric mucosa. (2) rhITF treatment significantly decreased the ulcer index and gastric acid output, but increased the GMBF, Hex and NO content in comparison with the control groups. In addition, rhITF also stimulated iNOSmRNA expression in the ulcer bed by situ hybridization analysis. Conclusion: rhITF can protect gastric mucosa against acute lesion, and enhance the healing of chronic gastric ulcer in the rats.This action may result from the inhibition of gastric acid output, increase of GMBF.Hex and NO content and rhITF stimulated iNOSmRNA expression.