Pancreatic Center, Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; Yangzhou Key Laboratory of Pancreatic Disease, Institute of Digestive Diseases, The Affiliated Hospital of Yangzhou University, Yangzhou University, China.
Department of Gastroenterology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China.
Biochem Biophys Res Commun. 2022 Apr 16;600:35-43. doi: 10.1016/j.bbrc.2022.02.019. Epub 2022 Feb 8.
The excessive inflammatory response mediated by macrophage is one of the key factors for the progress of acute pancreatitis (AP). Paeonol (Pae) was demonstrated to exert multiple anti-inflammatory effects. However, the role of Pae on AP is not clear. In the present study, we aimed to investigate the protective effect and mechanism of Pae on AP in vivo and vitro. In the caerulein-induced mild acute pancreatitis (MAP) model, we found that Pae administration reduced serum levels of amylase, lipase, IL-1β and IL-6 and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. And Pae decrease the ROS generated, restore mitochondrial membrane potential (ΔΨm), inhibit M1 macrophage polarization and NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs) in vitro. In addition, specific NLRP3 inhibitor MCC950 eliminated the protective effect of Pae on AP induced by caerulein in mice. Correspondingly, the inhibitory effect of Pae on ROS generated and M1 polarization was not observed in BMDMs with MCC950 in vitro. Taken together, our datas for the first time confirmed the protective effects of Pae on AP via the NLRP3 inflammasomes Pathway.
由巨噬细胞介导的过度炎症反应是急性胰腺炎 (AP) 进展的关键因素之一。丹皮酚（Pae）已被证明具有多种抗炎作用。然而，丹皮酚在 AP 中的作用尚不清楚。在本研究中，我们旨在研究丹皮酚对体内和体外 AP 的保护作用及其机制。在胆酸钠诱导的轻度急性胰腺炎 (MAP) 模型中，我们发现丹皮酚给药剂量依赖性地降低了血清淀粉酶、脂肪酶、IL-1β 和 IL-6 水平，并减轻了胰腺组织的组织病理学表现。并且丹皮酚减少了骨髓来源的巨噬细胞（BMDMs）中 ROS 的产生，恢复了线粒体膜电位（ΔΨm），抑制了 M1 巨噬细胞极化和 NLRP3 炎性体。此外，特异性 NLRP3 抑制剂 MCC950 消除了丹皮酚对胆酸钠诱导的小鼠 AP 的保护作用。相应地，在体外使用 MCC950 时，未观察到丹皮酚对 BMDMs 中 ROS 产生和 M1 极化的抑制作用。总之，我们的数据首次证实了丹皮酚通过 NLRP3 炎性体途径对 AP 的保护作用。
