Indomethacin alleviates cerulein-induced acute pancreatitis in mice by restoring autophagy flux
LOU Lijun
LI Renlong
LI Yan
LI Jing
KANG Xiaoyu
WANG Xiangping
PAN Yanglin
Abstract：Objective To investigate the effect of indomethacin on cerulein-induced acute pancreatitis(AP)in mice.Methods Twenty-eight C57BL/6 mice were randomly divided into control group,indomethacin group,cerulein group,and cerulein + indomethacin group.A mouse AP model was established by intraperitoneal injection of cerulein(50 μg/kg).Cerulein +indomethacin group was given two intraperitoneal injections of indomethacin(8 mg/kg)at 6 h and 0.5 h before the first injection of cerulein.The histopathological changes of pancreas were observed by HE staining and histopathological scores were performed.Serum amylase and lipase levels were detected.The number of MPO+ cells was detected by immunohistochemistry,the mRNA expression of inflammatory factors was detected by qPCR,the number of autophagic vacuoles in each group was detected by electron microscopy,and the expression of autophagy-related proteins LC3-Ⅱ and P62 was detected by Western blotting.Results Compared with the control group,the cerulein group showed an increase in histopathological scores(P<0.05),serum amylase and lipase levels(P<0.05),number of MPO+ cells and mRNA expression levels of inflammatory factors(P<0.05),number of autophagic vacuoles,and expression of LC3-Ⅱ and P62 proteins(P<0.05).Compared with the cerulein group,the cerulein + indomethacin group showed a decrease in inflammatory changes of pancreatic tissue,histopathological scores(P<0.05),serum amylase and lipase levels(P<0.05),number of MPO+ cells and mRNA expression levels of inflammatory factors(P<0.05),abnormal accumulation of autophagic vacuoles,and expression of LC3-Ⅱ and P62 proteins(P<0.05).Conclusion This study finds that indomethacin can alleviate cerulein-induced pancreatic tissue damage and improve impaired autophagic flux in mice,suggesting that indomethacin may exert its protective effect on AP in mice by restoring the impaired autophagic flux.
Keywords：acute pancreatitisindomethacinceruleinautophagy
Publication Date：2024-03-28
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：7( 263-269 )