Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
J Clin Biochem Nutr. 2011 Mar;48(2):117-21. doi: 10.3164/jcbn.10-73. Epub 2011 Feb 26.
Recent studies using small bowel endoscopy revealed that non-steroidal anti-inflammatory drugs including low-dose aspirin, can often induce small bowel injury. Non-steroidal anti-inflammatory drugs-induced small bowel mucosal injury involves various factors such as enterobacteria, cytokines, and bile. Experimental studies demonstrate that both mitochondrial disorders and inhibition of cyclooxygenases are required for development of non-steroidal anti-inflammatory drugs-induced small bowel injury. Mitochondrion is an organelle playing a central role in energy production in organisms. Many non-steroidal anti-inflammatory drugs directly cause mitochondrial disorders, which are attributable to uncoupling of oxidative phosphorylation induced by opening of the mega channel called mitochondrial permeability transition pore on the mitochondrial membrane by non-steroidal anti-inflammatory drugs. Bile acids and tumor necrosis factor-α also can open the permeability transition pore. The permeability transition pore opening induces the release of cytochrome c from mitochondrial matrix into the cytosol, which triggers a cascade of events that will lead to cell death. Therefore these mitochondrial disorders may cause disturbance of the mucosal barrier function and elevation of the small bowel permeability, and play particularly important roles in early processes of non-steroidal anti-inflammatory drugs-induced small bowel injury. Although no valid means of preventing or treating non-steroidal anti-inflammatory drugs-induced small bowel injury has been established, advances in mitochondrial studies may bring about innovation in the prevention and treatment of this kind of injury.
最近的小肠内镜研究表明，包括低剂量阿司匹林在内的非甾体抗炎药常常可诱导小肠损伤。非甾体抗炎药诱导的小肠黏膜损伤涉及多种因素，如肠细菌、细胞因子和胆汁。实验研究表明，线粒体功能障碍和环氧化酶抑制均是导致非甾体抗炎药诱导的小肠损伤的必要条件。线粒体是生物体内能量产生的核心细胞器。许多非甾体抗炎药可直接引起线粒体功能障碍，这归因于非甾体抗炎药通过打开线粒体内膜上称为线粒体通透性转换孔的巨型通道，导致氧化磷酸化解偶联。胆汁酸和肿瘤坏死因子-α也可打开通透性转换孔。通透性转换孔的打开诱导细胞色素 c 从线粒体基质释放到细胞质中，引发级联事件，导致细胞死亡。因此，这些线粒体功能障碍可能导致黏膜屏障功能紊乱和小肠通透性增加，在非甾体抗炎药诱导的小肠损伤的早期过程中发挥特别重要的作用。虽然尚未建立有效的预防或治疗非甾体抗炎药诱导的小肠损伤的方法，但线粒体研究的进展可能为这种损伤的预防和治疗带来创新。
