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


CONCLUSIONS
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.
Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, China. Electronic address: njglyy@163.com.
Mingdong
M
Liu
Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, China.
Liangliang
L
Shi
Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, China.
Xiaoping
X
Zou
Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, China.
Xi
X
Zheng
Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, China.
Feng
F
Zhang
Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, China.
Xiwei
X
Ding
Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, China.
Hao
H
Zhu
Department of Gastroenterology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, China.
Yonghua
Y
Shen
D055371:Acute Lung Injury / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D000590:Amino Acid Chloromethyl Ketones / Q000627:therapeutic use*; D000681:Amylases / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis; D061945:Caspase Inhibitors / Q000627:therapeutic use*; D007249:Inflammation / Q000209:etiology* / Q000517:prevention & control*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D008297:Male; D010183:Pancreatic Ducts / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D013656:Taurocholic Acid; D000681:Amylases; C505410:Casp3 protein, rat; D053148:Caspase 3
Acute pancreatitis-associated lung injury; Apoptosis; Caspase; Inflammation; zVAD-fmk