Naito Y, Yoshikawa T, Matsuyama K, Yagi N, Arai M, Nakamura Y, Nishimura S, Yoshida N, Kondo M
First Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
J Clin Gastroenterol. 1995;21 Suppl 1:S82-6.
Oxygen free radicals have been implicated in the pathogenesis of gastrointestinal mucosal injury. However, their effect on the quality of experimental gastric ulcer healing has not been investigated previously. Gastric ulcers were produced on the anterior wall of the stomach of rats by submucosal injection of 20% acetic acid. To investigate the role of oxygen radicals, rats with gastric ulcers were treated with scavengers for 6 weeks. Rats received either a daily dose of 20,000 U/kg of recombinant human Cu,Zn-SOD, a 1% solution of DMSO administered orally ad libitum, or 50 mg/kg/day of allopurinol administered orally. The quality of ulcer healing was evaluated by histologic and biochemical parameters: ulcer area, lipid peroxide levels, abnormality of regenerated mucosa, angiogenesis, and fibrosis as assessed by Azan staining, mucin content as assessed by the PAS-positive area, and polymorphonuclear leukocyte (PMN) infiltration. The treatments with SOD, DMSO, or allopurinol did not affect the ulcer area or lipid peroxide levels in the gastric mucosa, and SOD did not affect the histologic abnormality score, PMN infiltration in regenerated mucosa, the collagen fiber proliferation index, or the PAS-positive mucous score. DMSO and allopurinol significantly increased the collagen fiber proliferation index and the PAS-positive mucous score compared with controls. These results indicate that scavenging hydroxyl radicals or inhibiting xanthine oxidase enhances the quality but not the speed of gastric ulcer healing.
氧自由基与胃肠道黏膜损伤的发病机制有关。然而，它们对实验性胃溃疡愈合质量的影响此前尚未得到研究。通过在大鼠胃前壁黏膜下注射20%醋酸来制造胃溃疡。为了研究氧自由基的作用，给患有胃溃疡的大鼠用清除剂治疗6周。大鼠每日分别接受20000 U/kg的重组人铜锌超氧化物歧化酶（Cu,Zn-SOD）、随意口服给予的1%二甲基亚砜（DMSO）溶液或口服给予50 mg/kg/天的别嘌呤醇。通过组织学和生化参数评估溃疡愈合质量：溃疡面积、脂质过氧化物水平、再生黏膜异常、血管生成和纤维化（通过阿赞染色评估）、黏蛋白含量（通过过碘酸雪夫氏染色阳性面积评估）以及多形核白细胞（PMN）浸润。用SOD、DMSO或别嘌呤醇治疗均不影响胃黏膜的溃疡面积或脂质过氧化物水平，且SOD不影响组织学异常评分、再生黏膜中的PMN浸润、胶原纤维增殖指数或过碘酸雪夫氏染色阳性黏液评分。与对照组相比，DMSO和别嘌呤醇显著增加了胶原纤维增殖指数和过碘酸雪夫氏染色阳性黏液评分。这些结果表明，清除羟自由基或抑制黄嘌呤氧化酶可提高胃溃疡愈合的质量，但不能加快其愈合速度。
