• Pancreatology · Sep 2016

    Caspase inhibitor zVAD-fmk protects against acute pancreatitis-associated lung injury via inhibiting inflammation and apoptosis.

    • Mingdong Liu, Liangliang Shi, Xiaoping Zou, Xi Zheng, Feng Zhang, Xiwei Ding, Hao Zhu, and Yonghua Shen.
    • Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, China. Electronic address: njglyy@163.com.
    • Pancreatology. 2016 Sep 1; 16 (5): 733-8.

    Background/ObjectivesPulmonary apoptosis is an important pathogenic mechanism of acute lung injury induced by many factors. This study aims to investigate whether the caspase inhibitor zVAD-fmk has a protective effect against lung injury in the severe acute pancreatitis model (SAP) in rats.MethodsSeventy-two Sprague-Dawley rats were randomly divided into Sham, SAP, and SAP + zVAD-fmk groups. The SAP model was established by injection of 5% sodium taurocholate into the pancreatic duct. Animals were sacrificed at 3 h, 6 h, 12 h, and 24 h after operation and then HE staining analysis was performed to assess the lung injury. ELISA was used to detect the activity of myeloperoxidase (MPO) and the concentrations of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β). Western blotting was used to detect the expression of cleaved caspase-3 in the lung tissues.ResultsRats in SAP group showed obvious lung injury through pathologic examination. Pretreatment with zVAD-fmk significantly inhibited a post-SAP increase in the activation of MPO, TNF-α, IL-1β, and caspase-3, and decreased lung injury induced by SAP as determined by the pathologic score.ConclusionOur results suggest that apoptosis plays an important role in acute pancreatitis-associated lung injury (APALI), and inhibition of caspase activity may represent a new therapeutic approach for the treatment of APALI.Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

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