Sulaieva O N, Wallace J L
Klin Med (Mosk). 2017;95(3):222-7.
Despite the introduction of anti-inflammatory drugs that selectively inhibit cyclo-oxygenase-2 (COX-2), and potent inhibitors of gastric acid secretion, the gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) remain a significant clinical problem. Combined use of antisecretory drugs and COX-2 inhibitors is helpful to limit the damage in the proximal gastrointestinal tract (stomach and duodenum), but it increases the risk of injury of small intestine and colon. It was proven that proton pump inhibitors and H2 receptor antagonists significantly worsen NSAID-induced small intestinal damage and microbiota balance. Nowadays, there is no proven effective preventative or curative treatment for NSAID-induced enteropathy. The new strategy of gastrointestinal protection is based on the discovery of endogenous cytoprotective molecules such as hydrogen sulfide (H₂S). H2S is a gaseous mediator that produces strong cytoprotective and antioxidant effect on the gastrointestinal tract. The role of H₂S in promoting mucosal integrity, healing of tissue injury and resolution of inflammation has been well documented. In addition, H₂S stimulates productions of other cytoprotective molecules including prostaglandins, carbon monoxide and nitric oxide. Nowadays, the new generation of H₂S-releasing non-steroidal anti-inflammatory drugs is developed and tested in clinical trials. H₂S-NSAIDs possess enhanced anti-inflammatory activity and high gastrointestinal safety.
尽管已经引入了选择性抑制环氧化酶-2（COX-2）的抗炎药物以及强效胃酸分泌抑制剂，但非甾体抗炎药（NSAIDs）的胃肠道不良反应仍然是一个重大的临床问题。联合使用抗分泌药物和COX-2抑制剂有助于限制上消化道（胃和十二指肠）的损伤，但会增加小肠和结肠受伤的风险。事实证明，质子泵抑制剂和H2受体拮抗剂会显著加重NSAID引起的小肠损伤和微生物群平衡失调。目前，尚无经证实有效的NSAID诱导的肠病预防或治疗方法。胃肠道保护的新策略基于内源性细胞保护分子如硫化氢（H₂S）的发现。H2S是一种气体介质，对胃肠道具有强大的细胞保护和抗氧化作用。H₂S在促进黏膜完整性、组织损伤愈合和炎症消退中的作用已得到充分证明。此外，H₂S还能刺激包括前列腺素、一氧化碳和一氧化氮在内的其他细胞保护分子的产生。目前，新一代释放H₂S的非甾体抗炎药已研发出来并正在进行临床试验。H₂S-NSAIDs具有增强的抗炎活性和较高的胃肠道安全性。
