表皮生长因子促细胞增殖的量-效关系及对萎缩性胃炎大鼠胃黏膜的保护作用

Dose-related effect of EGF on the proliferation of human amnion cells and the protection effect of EGF to the chronic atropbic gastric mucosa in rats

目的探讨表皮生长因子(EGF)促细胞增殖的剂量-效应关系及对萎缩性胃炎(CAG)大鼠胃黏膜增生作用的影响。方法用不同浓度EGF对培养的人羊膜细胞进行不同时间段刺激, MTT法和蛋白印迹法(Western blot)检测细胞增殖情况及细胞外信号调节蛋白激酶(Erk1／2)变化结果;建立CAG大鼠模型,对CAG大鼠皮下注射EGF,12周后观察大鼠胃黏膜病理变化。结果剂量-时间-效应关系示EGF浓度10μg／L第3天时促细胞增殖率最高(42．4％,P<0．01),Western blot结果示EGF浓度10～60μg／L时磷酸化Erk1／2活性显著升高;动物实验示EGF治疗组胃黏膜腺体排列整齐规则,炎性细胞极少,明显好于对照组,治疗组(rhEGF和羊EGF)胃黏膜增殖细胞核抗原(PCNA)表达阳性的宽度分别为(77．70±4．16)μm和(75．60±2．92)μm,较对照组(54．40±4．54)μm明显增加(P<0．01)。结论EGF促细胞增殖及激活Erk1／2通路有明显的剂量或时间依赖性作用,EGF对SD大鼠萎缩性胃黏膜有保护性促增生作用。

Objective To explore the dose-related effect of epidermal growth factor（EGF）on the proliferation of human amnion cells（FL cells） and the protection effect of EGF to the atrophic gastric mucosa in rats. Methods FL cells were stimulated by EGF at different concentrations and time. The proliferation of FL cells was evaluated by MTT assay and the level of p-Erk1/2 protein was detected by Western blot. The chronic atrophic gastritis （CAG）of rats were treated with EGF subcutaneously per day and the pathological changes of the gastric mucosa were examined after 12 weeks. Results The proliferation rate of FL cells reached its peak on the third day at EGF concentration of 10 μg/L（42. 4% ,P〈0.01）. Expression of p-Erk1/2 protein was markedly elevated when concentrations of EGF were 10-60 μg/L. In the therapy groups, the gastric glands were rearranged in order and the inflammatory cells were less. The width of the expression of proliferating cell nuclear antigen（PCNA） of gastric mucosa were more in the therapy groups than in the control group[（77.70±4. 16）μm in rhEGF, （75.60 ± 2. 92）μm in sheep EGF vs （54. 40 ± 4. 54）μm in control, all P〈0.01]. Conclusions EGF promotes cell proliferation and p-Erk1/2 expression in a dose or time dependent manner. It has a protective proliferation effect on the atrophic gastric mucosa in SD rats.