title: Aspirin Protects against Acinar Cells Necrosis in Severe Acute Pancreatitis in Mice.
abstract: Aspirin has a clear anti-inflammatory effect and is used as an anti-inflammatory agent for both acute and long-term inflammation. Previous study has indicated that aspirin alleviated acute pancreatitis induced by caerulein in rat. However, the role of aspirin on severe acute pancreatitis (SAP) and the necrosis of pancreatic acinar cell are not yet clear. The aim of this study was to determine the effects of aspirin treatment on a SAP model induced by caerulein combined with Lipopolysaccharide. We found that aspirin reduced serum amylase and lipase levels, decreased the MPO activity, and alleviated the histopathological manifestations of pancreas and pancreatitis-associated lung injury. Proinflammatory cytokines were decreased and the expression of NF-κB p65 in acinar cell nuclei was suppressed after aspirin treatment. Furthermore, aspirin induced the apoptosis of acinar cells by TUNEL assay, and the expression of Bax and caspase 3 was increased and the expression of Bcl-2 was decreased. Intriguingly, the downregulation of critical necrosis associated proteins RIP1, RIP3, and p-MLKL was observed; what is more, we additionally found that aspirin reduced the COX level of pancreatic tissue. In conclusion, our data showed that aspirin could protect pancreatic acinar cell against necrosis and reduce the severity of SAP. Clinically, aspirin may potentially be a therapeutic intervention for SAP.
authors.affiliation: Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, China; Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou, China.
authors.forename: Guotao
authors.initials: G
authors.lastname: Lu
authors.affiliation: Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Tong
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou, China.
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Key Laboratory of Molecular Cardiovascular Science Ministry of Education, Institute of Cardiovascular Science, Peking University, Beijing, China.
authors.forename: Jinjiao
authors.initials: J
authors.lastname: Liu
authors.affiliation: Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, China.
authors.forename: Yiyuan
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Gao
authors.affiliation: Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, China; Department of Emergency, Zhejiang Provincial People's Hospital, Zhejiang, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Tu
authors.affiliation: Key Laboratory of Molecular Cardiovascular Science Ministry of Education, Institute of Cardiovascular Science, Peking University, Beijing, China.
authors.forename: Yuhui
authors.identifier: 0000-0003-2936-3377
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Cardiovascular Science Ministry of Education, Institute of Cardiovascular Science, Peking University, Beijing, China.
authors.forename: George
authors.initials: G
authors.lastname: Liu
authors.affiliation: Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, Jiangsu Province 210002, China.
authors.forename: Weiqin
authors.identifier: 0000-0002-8483-6264
authors.initials: W
authors.lastname: Li
mesh_terms: D061354:Acinar Cells / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001241:Aspirin / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D020690:GTPase-Activating Proteins / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009336:Necrosis / Q000188:drug therapy* / Q000378:metabolism; D010195:Pancreatitis / Q000188:drug therapy* / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D020690:GTPase-Activating Proteins; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; C490620:Ralbp1 protein, mouse; D051996:Transcription Factor RelA; D051028:bcl-2-Associated X Protein; C570694:MLKL protein, mouse; D011494:Protein Kinases; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C485615:Ripk3 protein, mouse; D053148:Caspase 3; D001241:Aspirin