| 抄録 |
The pathogenesis of ulceration and bleeding in the small intestine associated with use of nonsteroidal anti-inflammatory drugs（NSAIDs）is complex and multi-factorial. The primary location of the ulcers（distal jejunum and ileum）is suggestive of a role for enteric bacteria in the initiation of the damage following NSAID administration, as are the observations that germ-free animals do not develop enteropathy when given NSAIDs. Aside from well known detrimental effects of bacteria on healing of mucosal lesions, bacteria may contribute to NSAID-enteropathy through their roles in facilitating enterohepatic recirculation of NSAIDs, and through their effects of bile composition in the intestine. We have demonstrated that suppression of gastric acid secretion, with proton pump inhibitors or histamine H-2 antagonists, significantly worsens NSAID-enteropathy. Significant changes in enteric flora occur as a result of the suppression of acid secretion, and this contributes to the increased severity of intestinal damage when NSAIDs are administered. The increased damage may be in part related to an increase in the cytotoxicity of bile in animals treated with NSAIDs or with drugs that suppress acid secretion. Interestingly, when hydrogen sulfide（H2S）-releasing NSAID derivatives are administered, small intestinal damage is not observed（despite suppression of cyclooxygenase activity）and there is no increase in the cytotoxicity of bile. Ongoing studies are aimed at determining the precise changes in intestinal microbiota that contribute to the injury induced in the small intestine following NSAID administration. |
