Mechanism of NLRP3 Inflammasome Mediated Pyroptosis in Acute Pancreatitis - related Lung Injury / 胃肠病学
Chinese Journal of Gastroenterology
;
(12): 257-263, 2023.
Artículo
en Chino
| WPRIM
| ID: wpr-1016018
ABSTRACT
Background:
Pyroptosis is involved in the occurrence of acute pancreatitis, but its role in remote organ injury remains unclear.Aims:
To investigate the role and mechanism of NLRP3 inflammasome-dependent pyroptosis in acute pancreatitis- related lung injury.Methods:
Thirty-two male Sprague-Dawley rats were randomly divided into four groups control group, severe acute pancreatitis (SAP) group, Z-WEHD-FMK (caspase-1 inhibitor) group and disulfiram (GSDMD inhibitor) group. Experimental SAP was constructed by using 5% sodium taurocholate in the latter 3 groups. Serum levels of amylase, lipase, procalcitonin, and the myeloperoxidase (MPO) activity were determined; the severity of pancreatic and lung injuries was assessed by histopathology and lung wet/dry weight ratio; serum levels of pyroptosis-related inflammatory cytokines and the expressions of proteins involved in pyroptosis pathway in lung tissue were measured by ELISA method and immunohisto- chemistry and Western blotting, respectively.Results:
Compared with the control group, the serum biochemical indices, MPO activity, and interleukin (IL)-1β, IL-18 levels in SAP group were significantly increased with aggravated pancreatic and lung tissue injuries; meanwhile, the expressions of NLRP3, caspase-1 and GSDMD in lung tissue were significantly up- regulated (all P<0.05). Pretreatment with caspase-1 or GSDMD inhibitors reduced the severity of pancreatic and lung tissue injuries, improved the serum biochemical indices and MPO activity, and ameliorated the increased pyroptosis - related inflammatory cytokines and pyroptosis pathway - related proteins (all P<0.05).Conclusions:
NLRP3/caspase - 1/GSDMD pathway mediated pyroptosis plays an important role in acute pancreatitis-related lung injury, and inhibition of pyroptosis pathways might be a new direction for its treatment.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Idioma:
Chino
Revista:
Chinese Journal of Gastroenterology
Año:
2023
Tipo del documento:
Artículo
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