Caspase inhibitor zVAD-fmk protects against acute pancreatitis-associated lung injury via inhibiting inflammation and apoptosis |
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| Affiliation: | 1. Medical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom;2. Institute of Biotechnology, University of Helsinki, Helsinki, Finland;3. College of Life Sciences, University of Dundee, Dundee, United Kingdom;1. Department of Gastroenterology, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China;2. Department of Gastroenterology, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, China;1. Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA;2. Harvard Medical School, Boston, MA;3. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA;4. Department of Oncological Sciences, University of Utah, Salt Lake City, UT;5. Department of Pathology, Brigham and Women''s Hospital, Boston, MA;6. Department of Computational Biology and Biostatistics, Dana-Farber Cancer Institute, Boston, MA;7. Department of Pathology, Massachusetts General Hospital, Boston, MA;8. Novimmune SA, Geneva, Switzerland;9. Broad Institute of Harvard and MIT, Cambridge, MA;3. Roy J. Carver Department of Biochemistry, Biophysics & Molecular Biology, Iowa State University, Ames Iowa 50011;4. Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602;5. Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602;1. Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, Iowa, USA;2. Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, USA;3. Georgia Genomics and Bioinformatics Core and Institute of Bioinformatics, University of Georgia, Athens, Georgia, USA;4. Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA;5. Complex Carbohydrate Research Center, University of Georgia, Athens, Georgia, USA;1. Department of Emergency Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China;2. Department of Nephrology Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200092, China |
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| Abstract: | 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. |
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| Keywords: | Caspase zVAD-fmk Acute pancreatitis-associated lung injury Apoptosis Inflammation |
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