Ascites of rat experimental model of severe acute pancreatitis induces lung injury.
The molecular mechanisms that lead from acute pancreatitis (AP) to multiple organ failure remain to be clarified. We previously reported that ascitic fluids from a rat model of severe acute pancreatitis (pancreatitis-associated ascitic fluids, PAAF) transcriptionally activated endothelial cells and leukocytes in vitro. To clarify the role of ascitic fluids on the development of multiple organ failure in AP, we examined the effects of PAAF on the prognosis and immunohistologic findings in cerulein pancreatitis, an experimental model of mild pancreatitis in vivo. Intraperitoneal injection of PAAF decreased the survival rates in a dose-dependent manner. Histologically, destruction of vessels, alveolar septal thickening, interstitial hypertrophy, and infiltration of inflammatory cells were prominent in the lung of PAAF-injected rats. Transcription factor, nuclear factor KB (NF-kappaB) was activated and the mRNA levels of tumor necrosis factor-alpha and interleukin-1beta were increased in the lung of the PAAF-injected rats. The permeability index assessed by Evans blue assay and the lung myeloperoxidase activity levels were significantly higher in the PAAF-injected rats than in controls. Inhibition of NF-kappaB ameliorated the histologic findings and improved the survival rates. Our results suggest that PAAF play a role in the pathogenesis of lung injury in severe AP, at least in part through the activation of NF-kappaB.
Fujita
M
M
Department of Gastroenterology, Tohoku University School of Medicine, Sendai, Japan.
Masamune
A
A
Satoh
A
A
Sakai
Y
Y
Satoh
K
K
Shimosegawa
T
T
D000208:Acute Disease; D000818:Animals; D001201:Ascites / Q000150:complications*; D001202:Ascitic Fluid; D002108:Ceruletide; D004195:Disease Models, Animal; D005070:Evans Blue; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000235:genetics; D008168:Lung / Q000201:enzymology / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D009195:Peroxidase / Q000032:analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D007375:Interleukin-1; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D005070:Evans Blue; D002108:Ceruletide; D009195:Peroxidase