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目的:进一步明确叶酸抗萎缩性胃炎和阻断人胃癌发生发展的分子机理。方法:将25例慢性萎缩性胃炎(CAG)病人随机分组,分别用叶酸和安慰剂治疗半年,以放免法观察血浆和胃粘膜组织内叶酸浓度的变化,分别以H-SAM掺入,液闪计数法和HpaⅡ/Mspl酶解,Southern blot法研究其胃癌区、癌旁和外周正常区的总基因组DNA与c-myc癌基因甲基化水平的改变。结果:叶酸(FA)组萎缩性胃炎患者治疗后血浆FA含量明显上升,萎缩和肠化改善显著,两者呈同步变化;治疗后FA组DNA掺入甲基的量明显减少(P<0.01).即其总基因组DNA甲基化水平上升,与血浆叶酸的升高相一致;胃癌病人手术标本甲基化水平的分析显示:c-myc片段低甲基化者,叶酸水平明显低于正常甲基化者(P<0.05)。结论:叶酸对CAG的组织病理具有显著的改善作用。
Objective: To further clarify the molecular mechanism of folic acid against atrophic gastritis and block the development of human gastric cancer. METHODS: Twenty-five patients with chronic atrophic gastritis (CAG) were randomly divided into groups and treated with folic acid and placebo for half a year. Changes in plasma and gastric mucosal folate concentrations were observed by radioimmunoassay. H-SAM incorporation and liquid flash were used. Counting method and HpaII/Mspl digestion and Southern blot were used to study the changes of the methylation levels of total genomic DNA and c-myc oncogenes in gastric cancer, paraneoplastic and peripheral normal areas. RESULTS: After treatment with atrophic gastritis in patients with folic acid (FA), plasma FA levels increased significantly, and atrophy and intestinal metaplasia improved significantly. Both showed a synchronous change; the amount of methylated DNA in the FA group was significantly reduced after treatment (P<0.01). That is, its total genomic DNA methylation level increased, consistent with the increase of plasma folate; analysis of methylation levels of surgical specimens of gastric cancer patients: c-myc fragment hypomethylation, the level of folic acid was significantly lower than normal Basicizers (P < 0.05). Conclusion: Folic acid can significantly improve the histopathology of CAG.