Effects of c-Jun N-terminal kinase signaling pathway on severe acute pancreatitis-associated lung injury.
OBJECTIVE
The objective of this study was to investigate the effects of the c-Jun N-terminal kinase (JNK) signaling pathway on rats' acute pancreatitis-associated lung injury (APALI).


METHODS
Seventy-two Sprague-Dawley rats were randomly divided into 3 groups, namely, the sham operation (SO) group, the severe acute pancreatitis (SAP) group, and the SP600125 group. The SAP model was established by injection of 5% sodium taurocholate into the pancreatic duct. The samples were taken at 3, 6, 12, and 24 hours. Serum amylase, pathologic lesions of the pancreas and lung tissues, wet-to-dry weight ratio of the lung, myeloperoxidase (MPO) activity of the lung, tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), intercellular adhesion molecule 1 (ICAM-1), and p-JNK of lung tissues were detected.


RESULTS
The wet-to-dry weight ratio, MPO activity, and IL-1β, TNF-α, ICAM-1, and p-JNK levels in the SAP group significantly increased compared with those in the SO group. The scores of lung pathologic injury significantly increased, consistent with the APALI. The wet-to-dry weight ratio, MPO activity, IL-1β, TNF-α, ICAM-1, p-JNK expressions, and lung pathologic injury scores in the SP600125 group decreased compared with those in the SAP group. p-JNK was closely correlated with MPO activity, IL-1β, ICAM-1, and total scores of lung injury.


CONCLUSIONS
The JNK signaling pathway plays a critical role in APALI. On the other hand, application of a specific JNK inhibitor can contribute to alleviation of APALI.
Department of Gastroenterology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, PR China.
Mingdong
M
Liu
Liangliang
L
Shi
Min
M
Chen
Suyu
S
Chen
Xiaoping
X
Zou
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D004195:Disease Models, Animal; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D055370:Lung Injury / Q000201:enzymology / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications* / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013656:Taurocholic Acid; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000873:Anthracenes; D007375:Interleukin-1; D047428:Protein Kinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C432165:pyrazolanthrone; D013656:Taurocholic Acid; D009195:Peroxidase; D048031:JNK Mitogen-Activated Protein Kinases; D000681:Amylases