Oh T Y, Lee J S, Ahn B O, Cho H, Kim W B, Kim Y B, Surh Y J, Cho S W, Lee K M, Hahm K B
Dong-A Pharmaceutical Research Institute, Yongin, Kyunggi-do, Korea.
Gut. 2001 Sep;49(3):364-71. doi: 10.1136/gut.49.3.364.
Although antisecretory medications such as histamine type II receptor antagonists or proton pump inhibitors have been used to treat reflux oesophagitis, a considerable number of patients do not achieve complete mucosal healing or suffer from either sustained symptoms or ensuing complications, suggesting other damaging factors or impaired mucosal resistance are also involved in the pathogenesis of reflux oesophagitis.
The present study was designed to evaluate oxidative stress as the major pathogenic factor of reflux oesophagitis and to determine the usefulness of antioxidants in the treatment of reflux oesophagitis.
Reflux oesophagitis was induced by insertion of a 3 mm calibre ring into the duodenum, 1 cm distal to the ligament of Treitz, in Sprague-Dawley rats.
DA-9601, a novel antioxidant substance, significantly attenuated the gross and histopathological scores of reflux oesophagitis compared with those treated with ranitidine alone or reflux oesophagitis controls in a dose dependent manner. Only scattered erosions were observed in the antioxidant pretreated group but acid suppression by ranitidine was not effective in decreasing the severity of reflux oesophagitis. Significantly increased amounts of malondialdehyde (MDA), increased nuclear factor kappaB (NFkappaB) activation, and depletion of reduced glutathione (GSH) were observed in experimentally induced reflux oesophagitis. DA-9601 pretreatment attenuated the decrement in mucosal GSH levels and decreased MDA formation significantly. DA-9601 treatment caused significant reductions in activation of NFkappaB transcription factor, especially the p50 subunit, in accordance with the significantly higher levels of inhibitory protein of NFkappaB expression.
Reflux oesophagitis caused considerable levels of oxidative stress in the oesophageal mucosa and antioxidant treatment should be considered as supplementary therapy in the prevention or treatment of reflux oesophagitis with acid suppression.
尽管诸如组胺H2受体拮抗剂或质子泵抑制剂等抗分泌药物已被用于治疗反流性食管炎，但仍有相当数量的患者未能实现黏膜完全愈合，或遭受持续症状或后续并发症的困扰，这表明其他损伤因素或黏膜抵抗力受损也参与了反流性食管炎的发病机制。
本研究旨在评估氧化应激作为反流性食管炎的主要致病因素，并确定抗氧化剂在治疗反流性食管炎中的有效性。
通过在Sprague-Dawley大鼠的十二指肠（距Treitz韧带1 cm远侧）插入一个3 mm口径的环来诱导反流性食管炎。
新型抗氧化物质DA-9601与单独使用雷尼替丁治疗的组或反流性食管炎对照组相比，以剂量依赖的方式显著减轻了反流性食管炎的大体和组织病理学评分。在抗氧化剂预处理组中仅观察到散在的糜烂，但雷尼替丁的抑酸作用在减轻反流性食管炎的严重程度方面无效。在实验诱导的反流性食管炎中观察到丙二醛（MDA）含量显著增加、核因子κB（NFκB）激活增加以及还原型谷胱甘肽（GSH）耗竭。DA-9601预处理减轻了黏膜GSH水平的降低，并显著减少了MDA的形成。DA-9601治疗导致NFκB转录因子的激活显著降低，尤其是p50亚基，这与NFκB表达抑制蛋白的水平显著升高一致。
反流性食管炎在食管黏膜中引起相当程度的氧化应激，抗氧化剂治疗应被视为在抑酸预防或治疗反流性食管炎中的辅助疗法。
