DPP4 Inhibitor Attenuates Severe Acute Pancreatitis-Associated Intestinal Inflammation via Nrf2 Signaling
DPP4 Inhibitor Attenuates Severe Acute Pancreatitis-Associated Intestinal Inflammation via Nrf2 Signaling
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DPP4 抑制剂通过 Nrf2 信号传导减轻重症急性胰腺炎相关肠道炎症
DOI：
10.1155/2019/6181754
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发表时间：
2019-11-15
影响因子：
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通讯作者：
Chen, Gang
中科院分区：
文献类型：
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作者：
Zhou, Xiang;Wang, Weiming;Chen, Gang
重症急性胰腺炎（SAP）是一种高发病率、高死亡率的疾病，常并发多器官功能障碍综合征（MODS）。肠道是MODS的主要器官，与疾病的进展密切相关。在这项研究中，我们证明了DPP 4抑制剂西格列汀在体外和体内都能保护SAP相关的肠损伤。这些有益效果是通过抑制氧化应激和炎症反应实现的。此外，与对照SAP小鼠相比，西格列汀处理的SAP小鼠中，Nrf 2的表达被诱导，NF-κB的表达被降低。此外，我们使用Nrf 2 −/−小鼠来测试Nrf 2在西格列汀治疗SAP期间的保护作用;我们的结果表明，Nrf 2 −/−小鼠的胰腺和肠道损伤比野生型小鼠更严重。综上所述，西格列汀可能通过灭活Nrf 2-NF-κB通路抑制SAP诱导的高水平ROS。
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-κB 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-κB pathway.