非ステロイド性抗炎症剤による胃粘膜病変に関する臨床病理学的ならびに実験的研究

Abstract

The influence of nonsteroidal antiinflammatory drugs (NSAIDs) on the development of gastric mucosal lesions (GMLs) was investigated clinicopathologically in patients with rheumatoid arthritis (RA) and experimentally in rats treated with NSAIDs. Two hundred and seventy-three patients with RA including 248 patients under NSAIDs therapy were employed in this clinical study. GMLs were classified into two categories, gastritis and/or gastric erosion (GGE) and gastric ulcer (GU). Of 273 patients with RA, GMLs were found in 146 patients, consisting of 90 patients with GGE, 32 patients with GU and 24 patients with both GGE and GU. Frequencies of GMLs were 58% (143/248) in RA patients under NSAIDs therapy and 12% (3/25) in those without NSAIDs, indicating a close association between development of GMLs and treatment with NSAIDs. Interesting- ly, patients under rectal NSAIDs therapy also developed GMLs at an almost the same frequency as those under oral NSAIDs therapy. The development of GMLs was confirmed experimentally in rats given sodium diclofenate intrarectally, suggesting that rectal admin- istration of NSAIDs is not safe enough to prevent GMLs induced by NSAIDs. On the other hand, the use of NSAIDs prodrugs may reduce the incidence of GMLs. Acidity in gastric juice was increased in patients with GMLs. In NSAIDs-treated rats, H₂ receptor antago- nists (H₂-RAs) and proton pump inhibitor (PPI) were both effective in preventing GMLs. In the present clinical observation, PPI was superior to H₂-RAs in healing GU in the patients treated with NSAIDs. The gastric mucosal blood flow measured by laser Doppler flow meter was decreased in RA patients with GU. Multi-variate analysis using Cox's hazard model clarified that healing of GU induced by NSAIDs was influenced by Stein- brocker's class, by location and size of GU, and by medication for GU.