肠三叶因子在胃黏膜应激适应性细胞保护中的作用

Role of the intestinal trefoil factor in gastric mucosal adaptive cytoprotection to stress

目的 研究肠三叶因子 (ITF ,为三叶肽家族一员 )、转化生长因子α(TGFα)及环氧合酶 2(COX 2 )在水浸束缚应激 (WRS)大鼠胃黏膜中基因表达变化 ,探讨其在胃黏膜应激适应性细胞保护中的相互关系及作用。方法 采用重复WRS制作模型 ,动态监测胃黏膜血流量 (GMBF) ,大体及光镜下观察黏膜损伤程度 (UI)及组织学变化 ,RT PCR检测ITF、TGFα及COX 2基因表达变化 ,免疫组化染色进一步证实ITF ,TGFα表达。结果 单次应激造成胃黏膜广泛损伤 ,重复应激后胃黏膜产生适应性 ,胃黏膜血流量上升 ,损伤逐渐减轻 ,4次应激后 ,损伤指数降低为单次应激的 2 1.99% ,且胃腺区细胞增殖 ,ITF、TGFα基因表达增强 (分别为 0 .0 40± 0 .0 0 1比 0 .372± 0 .0 10 ,P <0 .0 1;0 .86± 0 .0 1比 0 .93± 0 .0 1,P <0 .0 1) ,免疫组化染色证实了二者的变化趋势 ,而COX 2表达逐渐减弱 (0 .45± 0 .0 2比 0 .2 2± 0 .0 1,P <0 .0 1)。结论 胃黏膜适应性细胞保护伴有细胞增殖 ,ITF、TGFα表达水平增强及COX 2表达水平逐渐减弱 ,表明三者在这一现象中有重要的调节作用。

Objective To observe the change of mucosal gene expression of intestinal trefoil factor (ITF, a member of trefoil peptides) and transforming growth factor α(TGFα) as well as cyclooxygenase-2 (COX-2) under water restrain stress (WRS) in rats and to investigate their relationship involved in gastric stress adaptation. Methods After Wistar rats were exposed to single or repeated WRS for 4 h every other day up to 6 days, gastric mucosal blood flow (GMBF) was measured by LDF-3 Flowmetery, the extent of gastric mucosal lesions was evaluated grossly and histologically, and the expression of ITF, TGFα, and COX-2 mRNA was determined by RT-PCR and further confirmed by immunohistochemistry. Results WRS applied once produced numerous gastric mucosal erosions, but with repeated WRS, the adaptation to WRS enhanced, the area of gastric mucosal lesions being reduced by 21.99% after four consecutive WRS. The adaptation to WRS was accompanied by increased GMBF and active cell proliferation in the neck region of gastric glands and by increased expression of ITF (0.372±0.010 vs. 0.040±0.001, P<0.01), TGFα(0.93±0.01 vs. 0.86±0.01, P<0.01). The result was demonstrated further by immunohistochemistry, while COX-2 mRNA was reduced (0.22±0.01 vs. 0.45±0.02, P<0.01). Conclusions Gastric adaptation to WRS injury involves three aspects, that is, enhanced cell proliferation, increased expression of ITF and TGFα, and reduced expression of COX-2 mRNA, which suggest they all play an important role in the adaptation.