Oh T Y, Lee J S, Ahn B O, Cho H, Kim W B, Kim Y B, Surh Y J, Cho S W, Hahm K B
Dong-A Pharmaceutical Research Institute, Yongin, Kyunggi-do, South Korea.
Free Radic Biol Med. 2001 Apr 15;30(8):905-15. doi: 10.1016/s0891-5849(01)00472-5.
The facts that the severity of reflux esophagitis cannot be accurately predicted on the basis of acid exposure and acid suppression treatment is not enough for the complete healing, suggested that other damaging factors might be involved in pathogenesis of reflux esophagitis.
The present study was designed to evaluate the oxidative stress as the major pathogenic factor of reflux esophagitis and the importance of antioxidant in treatment of reflux esophagitis.
Reflux esophagitis was induced by the insertion of small caliber ring (3 mm in diameter) into the duodenum 1 cm distal to the ligament of Treitz in rats.
DA-9601, a novel antioxidant substance, attenuated the gross esophagitis significantly compared to that treated with ranitidine, histamine-2 receptor antagonist (H2-RA), in a dose-dependent manner. Severe, hemorrhagic, and longitudinal ulcerations were developed in H2-RA pretreated group, whereas mildly scattered erosions were observed in antioxidant-pretreated group. Significantly increased amounts of malondialdehyde (MDA), increased NF-kappaB activation, and the mucosal depletion of reduced glutathione (GSH) were observed in the esophagus of reflux esophagitis. H2-RA treatment didn't affect the levels of GSH and MDA, whereas DA-9601 attenuated the decrement of the GSH levels and significantly decreased lipid peroxides in the esophagus. Antioxidants treatment showed significant reductions in the activation of NF-kappaB, inflammation-associated transcription factor, especially p50 component in accordance with significant higher levels of NF-kappaB repressor, IkappaBalpha expression.
Oxygen-derived free radicals seem to be one of the important mediators in generation of reflux esophagitis, which suggests that the combination of antioxidant and anti-secretory medications will be ideal and more beneficial in the prevention and treatment of reflux esophagitis than currently prescribed antisecretory treatment alone.
反流性食管炎的严重程度无法根据酸暴露情况准确预测，且抑酸治疗不足以实现完全愈合，这表明反流性食管炎的发病机制可能涉及其他损伤因素。
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以及抗氧化剂在反流性食管炎治疗中的重要性。
通过在大鼠Treitz韧带远端1 cm处的十二指肠插入小口径环（直径3 mm）诱导反流性食管炎。
新型抗氧化物质DA-9601与组胺-2受体拮抗剂（H2-RA）雷尼替丁治疗相比，能以剂量依赖方式显著减轻肉眼可见的食管炎。H2-RA预处理组出现严重的出血性纵向溃疡，而抗氧化剂预处理组仅观察到轻度散在糜烂。反流性食管炎大鼠食管中丙二醛（MDA）含量显著增加、NF-κB激活增强以及还原型谷胱甘肽（GSH）黏膜耗竭。H2-RA治疗不影响GSH和MDA水平，而DA-9601减轻了GSH水平的降低并显著降低食管中的脂质过氧化物。抗氧化剂治疗使炎症相关转录因子NF-κB的激活显著降低，尤其是p50成分，同时NF-κB抑制因子IkappaBalpha表达水平显著升高。
氧衍生自由基似乎是反流性食管炎发生的重要介质之一，这表明抗氧化剂与抗分泌药物联合使用在反流性食管炎的预防和治疗中比目前单独使用的抗分泌治疗更理想且更有益。
