title: Ligustrazine alleviates acute pancreatitis by accelerating acinar cell apoptosis at early phase via the suppression of p38 and Erk MAPK pathways.
abstract: OBJECTIVE
  This study aimed to investigate the role of ligustrazine on apoptosis and inflammatory reaction in acute pancreatitis.
  
  
  METHODS
  Rats and acinar cells were treated with caerulein to induce acute pancreatitis models. Cell models were treated with saline, p38 inhibitor, Erk inhibitor and ligustrazine. Then, the levels of TNF-α, IL-1β and IL-6 were determined by ELISA assay, the protein levels of p38, Erk1/2, p53 and cleaved caspase3 were determined by western blotting, and apoptosis were measured by flow cytometry. Rat models were treated with saline and ligustrazine. Plasma amylase and pancreatic myeloperoxidase activity and the levels of TNF-α, IL-1β and IL-6 in rats were determined. The protein levels of p38, Erk1/2, p53 and cleaved caspase3 in pancreas tissues were determined by western blotting, and pancreas tissues were also performed TUNEL staining to observe apoptosis status.
  
  
  RESULTS
  Ligustrazine downregulated the levels of TNF-α, IL-1β, IL-6. The protein levels of p38 and Erk were reduced by p38 inhibitor, Erk inhibitor and ligustrazine, while the levels of p53 and cleaved caspase 3 were upregulated. Apoptosis of AP acinar cells and cells in AP rat models was promoted after treated with ligustrazine. Plasma amylase and pancreatic myeloperoxidase activity in AP rat models were reduced by ligustrazine.
  
  
  CONCLUSIONS
  Ligustrazine alleviates acute pancreatitis by accelerating acinar cell apoptosis at early phase via the suppression on p38 and Erk MAPK pathways. It is capable of attenuating the severity of acute pancreatitis and may have a therapeutic effect on patients with acute pancreatitis.
authors.affiliation: North China University of Science and Technology Affiliated Hospital, Tangshan 063000, Hebei, China.
authors.forename: Jianli
authors.initials: J
authors.lastname: Chen
authors.affiliation: North China University of Science and Technology Affiliated Hospital, Tangshan 063000, Hebei, China.
authors.forename: Junmao
authors.initials: J
authors.lastname: Chen
authors.affiliation: North China University of Science and Technology Affiliated Hospital, Tangshan 063000, Hebei, China.
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Wang
authors.affiliation: North China University of Science and Technology Affiliated Hospital, Tangshan 063000, Hebei, China.
authors.forename: Changyou
authors.initials: C
authors.lastname: Wang
authors.affiliation: North China University of Science and Technology Affiliated Hospital, Tangshan 063000, Hebei, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Cao
authors.affiliation: North China University of Science and Technology Affiliated Hospital, Tangshan 063000, Hebei, China.
authors.forename: Yongkui
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: North China University of Science and Technology Affiliated Hospital, Tangshan 063000, Hebei, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: North China University of Science and Technology Affiliated Hospital, Tangshan 063000, Hebei, China.
authors.forename: Mingxin
authors.initials: M
authors.lastname: Cui
authors.affiliation: North China University of Science and Technology Affiliated Hospital, Tangshan 063000, Hebei, China.
authors.forename: Qiuyan
authors.initials: Q
authors.lastname: Shi
authors.affiliation: North China University of Science and Technology Affiliated Hospital, Tangshan 063000, Hebei, China. Electronic address: hb_zhanggz@yeah.net.
authors.forename: Guozhi
authors.initials: G
authors.lastname: Zhang
mesh_terms: D061354:Acinar Cells / Q000187:drug effects / Q000473:pathology*; D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010195:Pancreatitis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D011719:Pyrazines; D009195:Peroxidase; D048051:p38 Mitogen-Activated Protein Kinases; D000681:Amylases; C017953:tetramethylpyrazine
keywords: Acinar cell; Acute pancreatitis; Apoptosis; Erk; Ligustrazine; p38 MAPK