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

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

  • Pancreatology. 2016 Sep-Oct;16(5):733-8. doi: 10.1016/j.pan.2016.06.002.
Mingdong Liu 1,  Liangliang Shi 2,  Xiaoping Zou 2,  Xi Zheng 2,  Feng Zhang 2,  Xiwei Ding 2,  Hao Zhu 2,  Yonghua Shen 2
Affiliations

Affiliations

  • 1 Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, China. Electronic address: [email protected].
  • 2 Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, China.
PMID: 27324074 DOI: 10.1016/j.pan.2016.06.002
Abstract

Background/objectives: Pulmonary 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.

Methods: Seventy-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.

Results: Rats 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.

Conclusion: Our 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.

Keywords

Acute pancreatitis-associated lung injury; Apoptosis; Caspase; Inflammation; zVAD-fmk.

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