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Effect of Helicobacter pylori infection on bax protein expression in patients with gastric precancerous lesions
Hai-Feng Liu, Wei-Wen Liu, Dian-Chun Fang, Guo-An Wang, Xiao-Chun Teng
Hai-Feng Liu, Wei-Wen Liu, Dian-Chun Fang, Guo-An Wang, Xiao-Chun Teng, Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China
Supported by: the fund for Key Projects in the Army Medical and Health 9th 5-year Plan, and by the fund for Chongqing applied base research.
Correspondence to: Dr. Hai-Feng Liu, Department of Gastroenterology, Southwest Hospital, Third Military Medical University, 30 Gaotanyan Zhengjie, Shapingba District, Chongqing 400038, China. email@example.com
Received: July 31, 2002 Revised: August 5, 2002 Accepted: August 16, 2002 Published online: January 15, 2003
AIM: To evaluate the effect of Helicobacter pylori (H. pylori) infection on bax protein expression, and explore the role of H. pylori in the development of gastric carcinoma.
METHODS: H. pylori was examined by rapid urease test and Warthin-Starry method, and bax protein was examined by immunohistochemical staining in 72 patients with pre-malignant lesions.
RESULTS: Bax protein was expressed with different degree in intestinal metaplasia and gastric dysplasia, its positive rate being 63.9%. The positive rate of Bax protein expression in H. pylori-positive gastric precancerous lesions (72.3%) was significantly higher than that in H. pylori-negative gastric precancerous lesions (48.0%, x2 = 4.191, P < 0.05). H. pylori infection was correlated well with the expression of Bax protein in gastric precancerous lesions(r = 0.978, P < 0.01). After eradication of H. pylori, the positive rate of bax protein expression was significantly decreased in H. pylori-positive gastric precancerous lesions(x2 = 5.506, P < 0.05). In the persistent H. pylori infected patients, the positive rate of Bax protein expression was not changed.
CONCLUSION: H. pylori is involved in the expression of Bax gene. H. pylori infection increases the expression of Bax protein, this may be one of the mechanisms of H. pylori infection in the induction of gastric epithelial cell apoptosis. H. pylori might act as a tumor promoter in the genesis of gastric carcinoma. Eradication of H. pylori could inhibit the formation and development of gastric carcinoma.
Key Words: N/A
Citation: Liu HF, Liu WW, Fang DC, Wang GA, Teng XC. Effect of Helicobacter pylori infection on bax protein expression in patients with gastric precancerous lesions. Shijie Huaren Xiaohua Zazhi 2003; 11(1): 22-24
胃癌发生发展过程中不仅存在细胞的过度增生, 而且存在细胞凋亡的异常, 细胞凋亡与细胞增生平衡失调是胃癌发生的病理学基础[19-28]. H. pylori是胃癌的第一类致病因子, 其在胃癌发生中的作用已被广泛关注[1,2,8-14]. 我们以往的研究工作发现, H. pylori感染不仅可以刺激胃黏膜上皮细胞过度增生, 也可以诱导胃黏膜上皮细胞凋亡, H. pylori感染是引起胃黏膜上皮细胞增生和凋亡异常的重要机制之一; H. pylori感染后使胃黏膜上皮细胞增生和凋亡均明显增加, 必然会导致胃黏膜上皮细胞增生与凋亡的调节紊乱, 使胃黏膜上皮细胞不稳定性增加, 从而增加患胃癌的危险性[20,23,24,28]. 但是, H. pylori感染诱导胃黏膜上皮细胞凋亡及促进胃黏膜上皮细胞过度增生的机制目前尚不清楚.
Bax是编码Bcl-2相关X蛋白(Bcl-2 associated X protein, Bax)的基因. Bax蛋白与Bcl-2蛋白有21%的同源性, 具有对抗Bcl-2蛋白抑制细胞凋亡的作用. 研究发现Bcl-2/Bax两蛋白之间的比例是决定对细胞凋亡抑制作用强弱的关键因素, 因此认为Bax是重要的促细胞凋亡基因之一[29,30]. H. pylori感染是否通过影响Bax基因的表达调控胃黏膜上皮细胞增生和凋亡, 是一个值得探讨的问题, 因此, 我们对胃癌前病变组织中H. pylori感染与Bax蛋白表达的关系进行了研究. 研究发现, Bax蛋白在肠化生和异型增生组织中均有不同程度的表达, H. pylori阳性组胃癌前病变组织中Bax蛋白表达阳性率显著高于H. pylori阴性组, H. pylori感染与Bax阳性表达及分级呈正相关; H. pylori根除组胃癌前病变Bax蛋白阳性表达率较治疗前显著降低, 而H. pylori仍为阳性组胃癌前病变Bax蛋白阳性表达率与治疗前无变化. 表明H. pylori感染可以促进Bax蛋白的表达, 这可能是H. pylori感染诱导胃黏膜上皮细胞凋亡的主要机制, 导致胃黏膜上皮细胞增生与凋亡的调节紊乱, 从而使胃黏膜上皮细胞易于向恶性转化. 其原因可能是H. pylori感染继发炎症过程中释放多种细胞因子、自由基和一氧化氮, 这些物质可引起染色体损伤、基因突变; 也可能是H. pylori自身及其代谢产物有潜在的致癌活性[31-34].