大鼠胃黏膜萎缩过程中的组织学变化和p16、Bcl-2、增殖细胞核抗原表达

Histological Change and Expression of p16, Bcl-2 and Proliferating Cell Nuclear Antigen in Atrophic Gastric Mucosa in Rats

背景:慢性萎缩性胃炎尤其是胃窦萎缩性胃炎与胃癌关系密切。胃黏膜恶变过程中,细胞增殖与凋亡异常发挥重要作用。目的:研究大鼠胃黏膜萎缩过程中的组织学变化,以及p16、Bcl-2、增殖细胞核抗原(PCNA)表达情况,探讨这些调控因子的改变对萎缩性胃炎形成的影响。方法:以氨水、脱氧胆酸钠和乙醇三种损伤因素联合作用诱导慢性萎缩性胃炎。大鼠分为正常对照组和模型组,分别于2、4、6个月后处死。取胃黏膜行大体观察和组织学检查,以免疫组化方法检测胃窦黏膜p16、Bcl-2、PCNA表达。结果:模型组胃黏膜炎症细胞浸润明显;胃窦小凹增生,腺体层厚度和腺体数目明显减少;胃体病变较轻,仅于后期出现壁细胞数目减少。在胃窦黏膜萎缩过程中,p16表达逐渐降低,Bcl-2和PCNA表达逐渐升高。萎缩组p16表达较非萎缩组显著降低,Bcl-2、PCNA表达较非萎缩组显著升高。结论:多因素长期慢性刺激可致大鼠胃黏膜萎缩。模型大鼠胃黏膜细胞处于高增殖状态,抑癌基因p16蛋白表达低下,凋亡抑制基因Bcl-2蛋白高表达,萎缩性胃炎的发病与细胞增殖与凋亡失衡相关。

Chronic atrophic gastritis, especially antral atrophic gastritis, is closely related with gastric cancer. Dysregulation of cell proliferation and apoptosis plays an important role in the malignant change of gastric mucosa. Aims： To investigate the histological change and expression of p16, Bcl-2 and proliferating cell nuclear antigen （PCNA） in atrophic gastric mucosa in rats so as to appraise the effect of these regulators on the formation of atrophic gastritis. Methods： Chronic atrophic gastritis was induced by ammonia, sodium deoxycholate and alcohol administration. The rats were divided into normal control group and model group, and were sacrificed 2, 4 and 6 months later, respectively. Gastric mucosa was taken for the observation of morphological and histological changes. Expression of p16, Bcl-2 and PCNA in antral mucosa were determined by immunohistochemical method. Results： Gastric antral mucosa of the model rats showed obvious inflammatory cell infiltration with gastric pit hyperplasia, the thickness and number of glands decreased significantly; changes of gastric body mucosa were mild, only with the number of parietal cells reduced at the 6th month. During the process of antral mucosal atrophy, the expression of p16 decreased and that of Bcl-2 and PCNA increased gradually. Expression of p16 was lower and expression of Bcl-2 and PCNA was higher in atrophic group than those in non- atrophic group. Conclusions： Muhifactorial long term chronic stimulation may lead to gastric mucosa atrophy in rats. Gastric mucosa of model rat is in a hyper-proliferation status, with low protein expression of anti-oncogene p16 and high protein expression of apoptosis suppressor gene Bcl-2. Development of atrophic gastritis has some correlation with the imbalance between cell proliferation and apoptosis.