幽门螺杆菌感染对胃上皮细胞动力学影响的研究

Effects of H. pylori infection on cell kinetics of gastric epithelial cells

目的:研究幽门螺杆菌感染对胃上皮细胞的凋亡/增殖比及凋亡相关基因表达的影响,从细胞动力学角度来探讨幽门螺杆菌的致病机制。方法:采用免疫组织化学和TUNEL法检测胃黏膜上皮细胞增殖、凋亡和凋亡相关基因bcl-2、bax、c-Myc的表达变化,分析凋亡/增殖比、凋亡相关基因表达与幽门螺杆菌感染的关系。结果:幽门螺杆菌阳性胃溃疡、幽门螺杆菌阳性十二指肠球部溃疡、幽门螺杆菌阴性正常胃黏膜、幽门螺杆菌阳性慢性萎缩性胃炎、幽门螺杆菌阳性胃癌的胃上皮细胞凋亡/增殖比逐渐下降,依次为0.527±0.148、0.452±0.141、0.286±0.034、0.182±0.073、0.042±0.004(P<0.01),幽门螺杆菌阳性慢性浅表性胃炎与幽门螺杆菌阴性正常对照胃上皮细胞凋亡/增殖比差异无显著性(P>0.05)。Bax、c-Myc在幽门螺杆菌阳性慢性浅表性胃炎组中的表达明显高于幽门螺杆菌阴性慢性浅表性胃炎组(P<0.01);Bcl-2在幽门螺杆菌阳性和阴性的慢性浅表性胃炎均极少表达。结论:幽门螺杆菌可能通过影响Bax和c-Myc等凋亡相关基因表达而诱导胃上皮细胞凋亡,并进而导致胃黏膜上皮细胞动力学紊乱,这可能是幽门螺杆菌的致病机制之一。

Objective： To explore the effects of H. pylori infection on gastric epithelial cell kinetics and the expression of apoptosis related genes. Methods：One hundred and thirty-seven persons were enrolled and biopsy/operation specimens were taken for H. pylori detection by culture and histological assessments. Apoptotic cells in the specimens were counted in situ by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） method. Epithelial cell proliferation was detected by immunohistochemical analysis of the proliferating cell nuclear antigen （PCNA）. The expressions of apoptosis-related gene Bax, bcl-2, and c-myc were examined by immunohistochemistry in biopsy specimens of 30 patients with H. pylori-infected chronic superficial gastritis and 10 uninfected patients with chronic superficial gastritis. Results： Of 137 persons, 104 showed positive H. pylori. H. pylori infected patients with GU, DU had significantly higher apoptosis/proliferation ratio than persons with normal mucosa（P 〈 0.01 ）, and H.pylori （＋） patients with CAG, gastric cancer had significantly lower apoptosis/proliferation ratio than persons with normal mucosa（P 〈 0.01 ）. But there was no difference between H.pylori（＋） patients with CSG and persons with normal mucosa（P 〉 0.05）. Bax and c-Myc in H.pylori （＋） chronic superficial gastritis were significantly higher expressed than that in H.pylori （-） chronic superficial gastritis （P 〈 0.01 ）. The positive staining of Bcl-2 was not found both in H.pylori （＋） group and H.pylori（-） group. Condution： H.pylori may af- fect apoptosis through altering the expression of apoptosis-related gene Bax and c-myc with the result of imbalance between gastric epithelial apoptosis and proliferation, which might be one part of the pathogenetic mechanisms of H.pylori infection.