Mechanism of NLRP3 Inflammasome Mediated Pyroptosis in Acute Pancreatitis - related Lung Injury
10.3969/j.issn.1008-7125.2023.05.001
- Author:
Ying FENG
1
;
Meixia GUO
1
;
Haoyu XU
1
;
Bo SUN
1
;
Junming ZHOU
1
;
Minli LI
1
;
Xing CHEN
2
Author Information
1. Department of Gastroenterology, Eastern Theater Command General Hospital
2. Drug Instrument Supervision and Inspection Station, Wuxi Joint Logistics Support Center
- Publication Type:Journal Article
- Keywords:
Acute Lung Injury;
Acute Pancreatitis;
NLRP3 Inflammasome;
Pyroptosis
- From:
Chinese Journal of Gastroenterology
2023;28(5):257-263
- CountryChina
- Language:Chinese
-
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.
