转化生长因子-α对应激状态下胃粘膜适应性细胞保护的调节作用

Regulating role of the TGF-α on gene expression of in gastric mucosal and adaptive cytoprotection under stress

目的 研究转化生长因子 α(TGF α)对水浸束缚应激 (WRS)状态下大鼠胃粘膜乳癌相关肽 ( pS2 )、肠三叶因子 (ITF)基因表达、胃粘膜血流量 (GMBF)及适应性细胞保护的调节作用。方法 采用重复水浸束缚应激制作模型 ,动态监测胃粘膜血流量 ,大体及光镜下观察粘膜损伤程度(UI)及组织学变化 ,逆转录 多聚酶链反应 (RT PCR)检测TGFα、pS2 及ITF基因表达变化。结果 单次应激造成胃粘膜广泛损伤 ,重复应激后胃粘膜产生适应性 ,胃粘膜血流量上升 ,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%,并且胃腺区细胞增殖 ,TGF α、pS2 及ITF基因表达增强 [分别为 ( 0 .86± 0 .0 1 )vs( 0 .93± 0 .0 1 ) ,P <0 .0 1 ;( 0 .37± 0 .0 2 )vs( 0 .77± 0 .0 1 ) ,P <0 .0 1 ;( 0 .0 4 0± 0 .0 0 1 )vs( 0 .372± 0 .0 1 ) ,P <0 .0 1 ],TGFα 与 pS2 及ITF均成正相关。结论 胃粘膜适应性细胞保护伴有细胞增殖 ,TGFα 对应激状态下胃粘膜 pS2 、ITF基因表达。

Objective To determine the regulating role of the transforming growth factor alpha(TGF α)gene expression of pS 2, ITF(both are a member of trefoil factor family),GMBF(gastric mucosal blood flow)in gastric mucosal and adaptive cytoprotection under WRS in rats.Mothods Wistar rats were exposed to single or repeated WRS for 4h every other day for up to 6 days,GMBF was measured by LDF 3 Flowmeter,the extent of gastric mucosal lesions were evaluated grossly and histologically and for expression of TGF α,pS2,ITF mRNA as determined by RT PCR.Results WRS applied once produced numerous gastric mucosal erosions,but with repeated WRS,the adaptation to this WRS developed,the area of gastric mucosal lesions being reduced by 21.99% after four consecutive WRS,this adaptation to WRS was accompanied by increased GMBF and active cell proliferation in the neck region of gastric glands and by increased expression of TGF α mRNA0.86±0.01 vs 0.93±0.01,( P <0.01),pS2 mRNA 0.37±0.02 vs 0.77±0.01,( P <0.01),ITF mRNA 0.040±0.001 vs 0.372±0.01,( P <0.01),there were positive relationship between TGF α and pS2 or ITF.Conclusion Gastric adaptation to WRS injury involves enhanced cell proliferation,increased expression of TGF α,pS2,ITF mRNA and increased GMBF suggesting TGF α play an important regulating role in this phenomenen.