Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China.
Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China.
Oxid Med Cell Longev. 2019 Nov 15;2019:6181754. doi: 10.1155/2019/6181754. eCollection 2019.
Severe acute pancreatitis (SAP) is a challenging disease with high morbidity and mortality, often complicated by multiple organ dysfunction syndrome (MODS). The intestine, a major organ involved in MODS, correlates strongly with the evolution of the disease. In this study, we demonstrated that the DPP4 inhibitor, sitagliptin, protects SAP-associated intestinal injury both in vitro and in vivo. These beneficial effects were achieved by suppressing oxidative stress and inflammatory responses. Moreover, in sitagliptin-treated SAP mice, expression of Nrf2 was induced and that of NF-B was reduced, compared to the control SAP mice. In addition, we used Nrf2 mice to test the protective effect of Nrf2 during sitagliptin treatment of SAP; our results indicated that Nrf2 mice had greater pancreatic and intestinal injury than wild-type mice. Taken together, high levels of ROS induced by SAP may be inhibited by sitagliptin, possibly by inactivating the Nrf2-NF-B pathway.
严重急性胰腺炎（SAP）是一种具有高发病率和死亡率的挑战性疾病，常并发多器官功能障碍综合征（MODS）。肠道是 MODS 中涉及的主要器官，与疾病的演变密切相关。在这项研究中，我们证明了 DPP4 抑制剂西他列汀在体内和体外均能保护 SAP 相关的肠道损伤。这些有益作用是通过抑制氧化应激和炎症反应来实现的。此外，与对照 SAP 小鼠相比，在西他列汀治疗的 SAP 小鼠中，Nrf2 的表达被诱导，而 NF-B 的表达被降低。此外，我们使用 Nrf2 小鼠来测试 Nrf2 在西他列汀治疗 SAP 中的保护作用；我们的结果表明，Nrf2 小鼠的胰腺和肠道损伤比野生型小鼠更大。综上所述，SAP 引起的高水平 ROS 可能被西他列汀抑制，这可能是通过使 Nrf2-NF-B 途径失活来实现的。
