Digestive Disease Research Institute, Shariati Hospital, North-Kargar Ave., Tehran, 14117, Iran.
Dig Dis Sci. 2012 Feb;57(2):413-8. doi: 10.1007/s10620-011-1865-x. Epub 2011 Sep 1.
Despite the rich literature on GERD, its cause and reason for increased prevalence remain obscure. Currently accepted mechanisms leave many questions unanswered. Nitrite chemistry at the GEJ is well described for carcinogenesis. Recent epidemiological and animal data have linked nitrates to GERD. "Nitrate reductase" of oral bacteria converts nitrates to nitrites. We hypothesized that nitrate reductase activity is higher in patients with erosive GERD, delivering more nitrite at the gastroesophageal-junction for a given nitrate intake.
To compare oral nitrate reductase activity of erosive GERD patients with controls.
Patients with erosive GERD and controls without GERD were enrolled. After overnight fasting, nitrite of oral cavity contents was measured at 1-min intervals for 3 min while incubating a 10-mg nitrate-N/L solution in the mouth. Nitrate reductase activity was calculated and compared between groups.
Eleven cases (ten males, mean age: 42.6 ± 11.7 year) and ten controls (eight males, mean age: 37.6 ± 9.2 year) were enrolled. Mean nitrate reductase activity was 3.23 ± 0.99 vs. 2.30 ± 0.83 "μg nitrite-N formed/person/minute" in cases and controls, respectively (p = 0.03).
Oral nitrate reductase activity in erosive GERD patients is higher than controls. Therefore, any dietary nitrate load generates more nitrite in these patients. This excess nitrite at the gastroesophageal junction, may potentially contribute to the development of GERD. This is the first report linking oral nitrite production to erosive GERD in man. We suggest that a "nitrate hypothesis" may answer yet unanswered questions about GERD pathogenesis. If confirmed, it may change our understanding of mechanisms of GERD and provide novel therapeutic targets.
尽管 GERD 的相关文献丰富，但病因和患病率增加的原因仍不清楚。目前公认的机制仍有许多未解之谜。GEJ 的亚硝酸盐化学在致癌作用方面已有详细描述。最近的流行病学和动物数据将硝酸盐与 GERD 联系起来。口腔细菌的“硝酸盐还原酶”可将硝酸盐转化为亚硝酸盐。我们假设，在 GERD 患者中，硝酸盐还原酶活性更高，在摄入相同量硝酸盐的情况下，在胃食管交界处产生更多的亚硝酸盐。
比较侵蚀性 GERD 患者与对照组的口腔硝酸盐还原酶活性。
招募患有侵蚀性 GERD 的患者和没有 GERD 的对照组。患者在禁食过夜后，在口中孵育 10mg 硝酸盐-N/L 溶液的 3 分钟内，每隔 1 分钟测量口腔内容物中亚硝酸盐的含量。计算并比较两组之间的硝酸盐还原酶活性。
纳入 11 例（10 名男性，平均年龄：42.6 ± 11.7 岁）和 10 名对照组（8 名男性，平均年龄：37.6 ± 9.2 岁）。病例组和对照组的平均硝酸盐还原酶活性分别为 3.23 ± 0.99 和 2.30 ± 0.83“μg 亚硝酸盐-N 形成/人/分钟”（p = 0.03）。
侵蚀性 GERD 患者的口腔硝酸盐还原酶活性高于对照组。因此，任何饮食硝酸盐负荷在这些患者中都会产生更多的亚硝酸盐。胃食管交界处的这种过量亚硝酸盐可能有助于 GERD 的发展。这是首次将口腔亚硝酸盐生成与人类侵蚀性 GERD 联系起来的报告。我们建议，“硝酸盐假说”可能可以解释 GERD 发病机制中尚未解答的问题。如果得到证实，它可能会改变我们对 GERD 发病机制的理解，并提供新的治疗靶点。
