El-Demerdash E, El-Mesallamy H O, Abu-Zaid N M, Gad M Z
Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Drug Discov Ther. 2010 Aug;4(4):276-84.
Nitric oxide (NO) appears to play a critical role in modulating gastric mucosal defense. Administration of NO donors has been reported to protect the gastrointestinal mucosa against damage induced by several irritants. However, the possible role of NO in healing existing ulcers must be clarified further. Therefore, the present study was designed to assess the effect of modulation of NO on the healing of an indomethacin-induced peptic ulcer using a NO precursor, L-arginine, and a competitive inhibitor of NO synthase, L-NAME. Results of administering L-arginine were compared to those using nitroglycerin (NTG), an NO donor. Rats were injected with a single oral dose of indomethacin (30 mg/kg) and then treated with L-arginine (200 mg/kg, i.p.), NTG (1 mg/kg, i.p.) or L-NAME (15 mg/kg, i.p.) once daily for 7 d starting 4 h after the indomethacin injection. Gross lesion examination and histological assessment were done. NO, prostaglandin (PGE2), and mucin content in gastric tissue were detected. In addition, oxidative stress markers including glutathione (GSH) and lipid peroxides were measured. L-arginine and NTG almost completely healed indomethacin-induced ulceration as indicated by macroscopic and histological examination, restoration of normal levels of NO and GSH, and a significant attenuation of the increase in PGE2 and lipid peroxides induced by indomethacin. In contrast, L-NAME was found to exacerbate mucosal damage. In conclusion, the present study provides further evidence for the role of NO in gastric ulcer healing and it suggests an alternative path to treating the universal problem of non-steroidal anti-inflammatory-drug-induced gastropathy.
一氧化氮（NO）似乎在调节胃黏膜防御中起关键作用。据报道，给予NO供体可保护胃肠道黏膜免受多种刺激物所致的损伤。然而，NO在现有溃疡愈合中的可能作用仍需进一步阐明。因此，本研究旨在使用NO前体L-精氨酸和NO合酶竞争性抑制剂L-NAME，评估调节NO对吲哚美辛诱导的消化性溃疡愈合的影响。将给予L-精氨酸的结果与使用NO供体硝酸甘油（NTG）的结果进行比较。给大鼠单次口服吲哚美辛（30 mg/kg），然后在吲哚美辛注射后4小时开始，每天一次腹腔注射L-精氨酸（200 mg/kg）、NTG（1 mg/kg）或L-NAME（15 mg/kg），持续7天。进行大体病变检查和组织学评估。检测胃组织中的NO、前列腺素（PGE2）和黏蛋白含量。此外，测量包括谷胱甘肽（GSH）和脂质过氧化物在内的氧化应激标志物。宏观和组织学检查表明，L-精氨酸和NTG几乎完全治愈了吲哚美辛诱导的溃疡，使NO和GSH恢复到正常水平，并显著减轻了吲哚美辛诱导的PGE2和脂质过氧化物的增加。相反，发现L-NAME会加重黏膜损伤。总之，本研究为NO在胃溃疡愈合中的作用提供了进一步的证据，并提示了一条治疗非甾体抗炎药所致胃病这一普遍问题的替代途径。
