Inhibition of Caspase-11-Mediated Pyroptosis Alleviates Acute Kidney Injury Associated with Severe Acute Pancreatitis in Rats. Issue 1 (1st January 2023)

• Record Type: Journal Article
• Authors: Shao, Yang; Li, Chang; Jiang, Yingjian; Li, Hongbo; Tang, Xuefei; Gao, Zhaoyu; Zhang, Dianliang
• Is Part Of: Journal of investigative surgery. Volume 36:Issue 1(2023)
• Page Start: 1
• Page End: 7
• Publication Date: 2023-01-01
• Subjects: caspase-11 -- pyroptosis -- severe acute pancreatitis -- acute kidney injury -- wedelolactone; Surgery -- Research -- Periodicals; Research; Surgery; Surgical Procedures, Operative; 617.075
• DOI: 10.1080/08941939.2022.2142868
• Languages: English
• ISSNs: 0894-1939

Abstract

Abstract: Background: Acute kidney injury (AKI) is a common complication in patients with severe acute pancreatitis (SAP). Caspase-11-mediated pyroptosis is essential for the progression of multiple diseases, but its role in SAP-induced AKI remains unknown. Aims: This research investigated whether caspase-11-mediated pyroptosis is involved in SAP-induced AKI and whether inhibiting caspase-11-mediated pyroptosis improves SAP-induced AKI. Methods: A rat model of SAP with AKI was established by slowly injecting 5% sodium taurocholate into the biliopancreatic duct, then wedelolactone (25 or 50 mg/kg), an inhibitor of caspase-11, was injected through the intra-peritoneum 1 and 6 h after SAP induction. Serum biochemical indexes, including serum amylase, lipase, interleukin (IL)-6, blood urea nitrogen (BUN), tumor necrosis factor (TNF)-α, and creatinine (Cr) in rats, were evaluated using biochemical test kits. Caspase-11 and gasdermin D (GSDMD) expression in the kidney tissues was evaluated by western blotting and immunohistochemical staining. IL-1β and IL-18 levels in kidney tissues were detected by ELISA kits. Furthermore, histopathological alterations of pancreas and kidney were assessed by H&E staining. Results: The serum biochemical indexes and pyroptosis-related proteins in kidney tissues were significantly increased after SAP induction. Furthermore, wedelolactone decreased the expression of pyroptosis-linked proteins in kidney tissues, reduced serum lipase, amylase, IL-6, TNF-α, BUN, and Cr, and ameliorated the renal and pancreatic histological damage in SAP rats. Conclusion: Caspase-11-mediated pyroptosis contributes to SAP-induced AKI, and targeting caspase-11-mediated pyroptosis might be a novel treatment strategy for SAP-induced AKI.