PDF(Sci-hub)
Abstract：
Recent advances in small-bowel endoscopy such as capsule endoscopy have shown that non-steroidal anti-inflammatory drugs (NSAIDs) frequently damage the small intestine, with the prevalence rate of mucosal breaks of around 50% in chronic users. A significant proportion of patients with NSAIDs-induced enteropathy are asymptomatic, but some patients develop symptomatic or complicated ulcers that need therapeutic intervention. Both inhibition of prostaglandins due to the inhibition of cyclooxygenases and mitochondrial dysfunction secondary to the topical effect of NSAIDs play a crucial role in the early process of injury. As a result, the intestinal barrier function is impaired, which allows enterobacteria to invade the mucosa. Gram-negative bacteria and endogenous molecules coordinate to trigger inflammatory cascades via Toll-like receptor 4 to induce excessive expression of cytokines such as tumor necrosis factor-α and to activate NLRP3 inflammasome, a multiprotein complex that processes pro-interleukin-1β into its mature form. Finally, neutrophils accumulate in the mucosa, resulting in intestinal ulceration. Currently, misoprostol is the only drug that has a proven beneficial effect on bleeding small intestinal ulcers induced by NSAIDs or low-dose aspirin, but its protection is insufficient. Therefore, the efficacy of the combination of misoprostol with other drugs, especially those targeting the innate immune system, should be assessed in the next step.
摘要：
胶囊内镜等小肠内镜的最新进展表明，非甾体抗炎药（NSAIDs）经常损害小肠，慢性使用者粘膜破裂的患病率约为50%。相当比例的NSAIDs引起的肠病患者无症状，但是一些患者会出现症状性或复杂性溃疡，需要治疗干预。由于环加氧酶的抑制引起的前列腺素的抑制和NSAIDs局部作用继发的线粒体功能障碍在损伤的早期过程中起着至关重要的作用。因此,肠道屏障功能受损，允许肠杆菌侵入粘膜。革兰氏阴性菌和内源性分子协同作用，通过Toll样受体4触发炎症级联反应，诱导肿瘤坏死因子-α等细胞因子的过度表达，并激活NLRP3炎性体，将前白细胞介素-1β加工成其成熟形式的多蛋白复合物。最后,中性粒细胞在粘膜中积聚，导致肠道溃疡。目前,米索前列醇是唯一一种对NSAIDs或低剂量阿司匹林引起的出血性小肠溃疡具有有益作用的药物，但保护力度不够。因此,米索前列醇与其他药物联合使用的疗效，尤其是那些针对先天免疫系统的，应该在下一步进行评估。
