表皮生长因子及其受体、转化生长因子-α在实验性胃溃疡愈合中的作用

Healing Effects of EGF,EGFR and TGF-α in Experimental Gastric Ulcer

目的探讨胃黏膜表皮生长因子(epidermal growth factor,EGF)及其受体(epidermal growthfactor receptor,EGFR)、转化生长因子-α(transforming growth factor-alpha,TGF-α)在大鼠胃溃疡愈合中的变化及意义。方法胃前壁黏膜下注射冰乙酸制备大鼠胃溃疡模型,免疫组织化学法检测溃疡组(42只)和正常组(6只)大鼠胃黏膜EGF、EGFR、TGF-α的表达,测量各指标的积分光密度值。结果 EGF、TGF-α以胞浆表达为主,EGFR以胞膜表达为主,三者均可见壁细胞、内分泌细胞阳性表达,阳性信号以靠近黏膜肌层为主。EGF、EGFR阳性细胞在溃疡术后1d即有增多(P<0.05或P<0.01),TGF-α于溃疡术后2d增多较为明显(P<0.01),之后均呈渐强趋势,EGFR阳性细胞在溃疡术后6d表达最强,EGF、TGF-α阳性细胞于溃疡术后10d积分光密度值达到高峰,溃疡愈合后期三种指标积分光密度值均有降低,但仍显著高于正常组(P<0.01)。结论大鼠胃溃疡自愈时期胃黏膜能特异性表达内源性EGF、EGFR、TGF-α,三者共同参与了胃溃疡愈合过程。

Objective To investigate the significance of EGF,EGFR and TGF-α in gastric mucosa during healing of experimental gastric ulcer of rats.Methods Acetic acid-induced ulcers were caused by injecting acetic acid to submucosa of gastric anterior wall.The expressions of EGF,EGFR and TGF-α in gastric ulcer group（n=42）and normal group（n=6）were detected by immunohistochemistry（IHC）and semi-quantity was analyzed with integral optical density（IOD）value.Results The locations of three above proteins had similar characteristics,which showed more stronger expression near muscularis mucosa,and some positive matters were observed in parietal and endocrine cells.EGF,TGF-α proteins were mainly in the cytoplasm of positive cells,whereas EGFR expressed on the cell membrane else.EGF and EGFR increased on the first day after ulcer operation（P0.01 or P 0.05）and TGF-α obviously increased on the 2nd day in ulcer group（P0.01）.Then the above proteins showed a gradually stronger expressional tendency.EGFR positive matters express strongest on the 6th day afte ulcer operation whereas the expression of EGF and TGF-α reached peak on the 10th day.In the later stage of ulcer healing,IOD values of EGF,EGFR and TGF-α all showed gradual decrease,but maintained a higher expression level（P0.01）.Conclusion Rat gastric mucosa could specifically express EGF,EGFR and TGF-α,which co-participate in the gastric ulcer healing.