DPP4 Inhibitor Attenuates Severe Acute Pancreatitis-Associated Intestinal Inflammation via Nrf2 Signaling

  • Oxid Med Cell Longev. 2019 Nov 15;2019:6181754. doi: 10.1155/2019/6181754.
Xiang Zhou  1 ,  Weiming Wang  1 ,  Cheng Wang  2 ,  Chenlei Zheng  1 ,  Xiangxiang Xu  1 ,  Xiaofeng Ni  1 ,  Shanshan Hu  1 ,  Binbin Cai  1 ,  Linxiao Sun  1 ,  Keqing Shi  1  2 ,  Bicheng Chen  1  2 ,  Mengtao Zhou  1  2 ,  Gang Chen  1  2
Affiliations
  • 1. Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 Zhejiang Province, China.
  • 2. 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.
PMID: 31827684 DOI: 10.1155/2019/6181754
Abstract

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.

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