Ligustrazine alleviates acute pancreatitis by accelerating acinar cell apoptosis at early phase via the suppression of p38 and Erk MAPK pathways

被引:37
作者
Chen, Jianli [1 ]
Chen, Junmao [1 ]
Wang, Xiaotao [1 ]
Wang, Changyou [1 ]
Cao, Wenbin [1 ]
Zhao, Yongkui [1 ]
Zhang, Bo [1 ]
Cui, Mingxin [1 ]
Shi, Qiuyan [1 ]
Zhang, Guozhi [1 ]
机构
[1] North China Univ Sci & Technol, Affiliated Hosp, South Jianshe Rd 73, Tangshan 063000, Hebei, Peoples R China
关键词
Ligustrazine; Acute pancreatitis; Acinar cell; Apoptosis; Erk; p38; MAPK; OXIDATIVE STRESS; NECROSIS; INJURY; ALPHA; RAT; INHIBITION; INDUCTION; MECHANISM; CYTOKINES; KINASES;
D O I
10.1016/j.biopha.2016.04.048
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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-alpha, IL-1 beta 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-alpha, IL-1 beta 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-alpha, IL-1 beta, 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. Conclusion: 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. (C) 2016 Elsevier Masson SAS. All rights reserved.
引用
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页码:1 / 7
页数:7
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