Indomethacin inhabits the NLRP3 inflammasome pathway and protects severe acute pancreatitis in mice
Indomethacin inhabits the NLRP3 inflammasome pathway and protects severe acute pancreatitis in mice
复制标题
吲哚美辛抑制 NLRP3 炎症小体通路并保护小鼠重症急性胰腺炎
DOI：
10.1016/j.bbrc.2017.08.060
复制
发表时间：
2017-11-04
影响因子：
3.1
通讯作者：
Li, Weiqin
中科院分区：
文献类型：
--
作者：
Lu, Guotao;Pan, Yiyuan;Li, Weiqin
临床研究证实，吲哚美辛（Indo）能有效降低内镜逆行胰胆管造影术后胰腺炎（PEP）的发生率和严重程度。然而，Indo在重症急性胰腺炎（SAP）中的作用尚不清楚。本研究旨在探讨Indo对雨蛙素联合脂多糖诱导的SAP模型的影响。腹腔注射Indo后，SAP的严重程度以及血清淀粉酶、脂肪酶和促炎细胞因子的水平均降低。胰腺组织中NLRP 3炎性体通路（NLRP 3、ASC和IL-1 β）的mRNA和蛋白水平下调。在体外实验中，通过分离小鼠胰腺腺泡细胞（PACs），我们发现Indo能显著减少PACs的乳酸脱氢酶（LDH）分泌，提高细胞活性，并抑制PACs的NLRP 3炎性体通路。以上结果表明，Indo可通过抑制NLRP 3通路保护胰腺腺泡细胞免受损伤，从而减轻SAP的严重程度。(C)2017由Elsevier Inc.出版
Clinical studies have confirmed that indomethacin (Indo) can reduce the incidence and severity of post-endoscopicretrogradecholangio-pancreatography pancreatitis (PEP) effectively. However, the role of Indo on severe acute pancreatitis (SAP) is not clear. In the present study, we aimed to explore the effects of Indo treatment on SAP model induced by caerulein combined with lipopolysaccharide. After intraperitoneal injection of Indo in mice, both the severity of SAP and the serum levels of amylase, lipase, and proinflammatory cytokines were decreased. Furthermore, the mRNA and protein levels of NLRP3 inflammasome pathway (NLRP3,ASC and IL-1 beta) in pancreatic tissues were down-regulated. In vitro experiments, by isolating the pancreatic acinar cells (PACs) from mice, we found that Indo significantly reduced lactate dehydrogenase(LDH) excretion, increased the cell activity, and inhibited the NLRP3 inflammasome pathway of PACs. Taken together, our data showed that Indo could protect pancreatic acinar cell from injury by inhabiting NLRP3 pathway and decreased the severity of SAP accordingly. (C) 2017 Published by Elsevier Inc.