Inducible nitric oxide synthase, nitrotyrosine, and apoptosis in Helicobacter pylori gastritis: effect of antibiotics and antioxidants.
Inducible nitric oxide synthase, nitrotyrosine, and apoptosis in Helicobacter pylori gastritis: effect of antibiotics and antioxidants.
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发表时间：
1996-07
期刊：
影响因子：
11.2
通讯作者：
E. Mannick;L. Bravo;G. Zarama;J. Realpe;X.‐J. Zhang;B. Ruiz;E. Fontham;R. Mera;M. Miller;P. Correa
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作者：
E. Mannick;L. Bravo;G. Zarama;J. Realpe;X.‐J. Zhang;B. Ruiz;E. Fontham;R. Mera;M. Miller;P. Correa
幽门螺杆菌感染是已知的胃癌危险因素。我们假设幽门螺杆菌感染会导致活性氮物种一氧化氮和过氧亚硝酸盐的持续产生，作为宿主免疫反应的一部分。我们进一步假设，幽门螺杆菌感染会导致胃上皮细胞凋亡增加，这可能是对自由基介导的DNA损伤的反应。应用免疫组织化学方法，对84例哥伦比亚非萎缩性胃炎患者幽门螺杆菌感染治疗前后的胃窦活检组织进行染色和评分。我们检测了诱导型一氧化氮合酶(INOS)的表达；硝基酪氨酸，过氧亚硝酸根的标记；以及DNA片段化，细胞凋亡的标记。患者接受三联疗法(阿莫西林500 mg，每日3次，疗程2周；甲硝唑，每日3次，400 mg，疗程2周；次水杨酸铋262 mg，每日4次，疗程2周，然后每天262 mg，疗程4-12个月)。根除幽门螺杆菌感染后，诱导型一氧化氮合酶和硝基酪氨酸染色显著减少，细胞凋亡率略有减少。饮食中补充β-胡萝卜素(每天30毫克，持续4-12个月)可显著降低iNOS的染色。补充抗坏血酸(每天两次，每次1克，持续4-12个月)可显著减少硝基酪氨酸染色。在补充抗坏血酸或β-胡萝卜素的患者中，有减少细胞凋亡的趋势，但这在统计学上没有显著意义。我们的结论是，幽门螺杆菌感染伴随着内源性活性氮中间产物的形成，这可能有助于DNA损伤和细胞凋亡。除了抗菌治疗外，饮食中补充β-胡萝卜素和抗坏血酸可以防止这些潜在致癌物的形成。
Helicobacter pylori infection is a known risk factor for gastric cancer. We hypothesized that H. pylori infection would lead to the sustained production of the reactive nitrogen species nitric oxide and peroxynitrite as part of the host immune response. We further hypothesized that H. pylori infection would lead to increased apoptosis of gastric epithelial cells, possibly in response to free radical-mediated DNA damage. Using immunohistochemistry, we stained and scored gastric antral biopsies from 84 Colombian patients with nonatrophic gastritis before and after treatment for H. pylori infection. We examined expression of inducible nitric oxide synthase (iNOS); nitrotyrosine, a marker for peroxynitrite; and DNA fragmentation, a marker for apoptosis. Patients were treated with triple therapy (amoxicillin, 500 mg three times a day for 2 weeks; metronidazole, 400 mg three times a day for 2 weeks; and bismuth subsalicylate, 262 mg four times a day for 2 weeks, followed by 262 mg every day for 4-12 months). Eradication of H. pylori infection resulted in a significant reduction in iNOS and nitrotyrosine staining and a marginally significant reduction in apoptosis. Dietary supplementation with beta-carotene (30 mg every day for 4-12 months) resulted in a significant decrease in iNOS staining. Supplementation with ascorbic acid (1 g twice a day for 4-12 months) led to a significant reduction in nitrotyrosine staining. In patients supplemented with either ascorbic acid or beta-carotene, there was a trend toward a reduction in apoptosis, but this was not statistically significant. We conclude that H. pylori infection is accompanied by the formation of endogenous reactive nitrogen intermediates, which may contribute to DNA damage and apoptosis. In addition to antimicrobial therapy, dietary supplementation with beta-carotene and ascorbic acid may prevent the formation of these potential carcinogens.