Inhibition of Caspase-11-Mediated Pyroptosis Alleviates Acute Kidney Injury Associated with Severe Acute Pancreatitis in Rats
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-...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-01-01
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| Series: | Journal of Investigative Surgery |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/08941939.2022.2142868 |
| _version_ | 1827817146725433344 |
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| author | Yang Shao Chang Li Yingjian Jiang Hongbo Li Xuefei Tang Zhaoyu Gao Dianliang Zhang |
| author_facet | Yang Shao Chang Li Yingjian Jiang Hongbo Li Xuefei Tang Zhaoyu Gao Dianliang Zhang |
| author_sort | Yang Shao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T00:30:16Z |
| format | Article |
| id | doaj.art-7ff65eb932724842a92245d33d850074 |
| institution | Directory Open Access Journal |
| issn | 0894-1939 1521-0553 |
| language | English |
| last_indexed | 2024-03-12T00:30:16Z |
| publishDate | 2023-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Investigative Surgery |
| spelling | doaj.art-7ff65eb932724842a92245d33d8500742023-09-15T10:21:30ZengTaylor & Francis GroupJournal of Investigative Surgery0894-19391521-05532023-01-013611710.1080/08941939.2022.21428682142868Inhibition of Caspase-11-Mediated Pyroptosis Alleviates Acute Kidney Injury Associated with Severe Acute Pancreatitis in RatsYang Shao0Chang Li1Yingjian Jiang2Hongbo Li3Xuefei Tang4Zhaoyu Gao5Dianliang Zhang6Qingdao Medical College, Qingdao UniversityDepartment of The First General Surgery, Qingdao Municipal Hospital Affiliated to Qingdao UniversityDepartment of The First General Surgery, Qingdao Municipal Hospital Affiliated to Qingdao UniversityDepartment of The First General Surgery, Qingdao Municipal Hospital Affiliated to Qingdao UniversityQingdao Medical College, Qingdao UniversityQingdao Medical College, Qingdao UniversityDepartment of The First General Surgery, Qingdao Municipal Hospital Affiliated to Qingdao UniversityBackground: 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.http://dx.doi.org/10.1080/08941939.2022.2142868caspase-11pyroptosissevere acute pancreatitisacute kidney injurywedelolactone |
| spellingShingle | Yang Shao Chang Li Yingjian Jiang Hongbo Li Xuefei Tang Zhaoyu Gao Dianliang Zhang Inhibition of Caspase-11-Mediated Pyroptosis Alleviates Acute Kidney Injury Associated with Severe Acute Pancreatitis in Rats Journal of Investigative Surgery caspase-11 pyroptosis severe acute pancreatitis acute kidney injury wedelolactone |
| title | Inhibition of Caspase-11-Mediated Pyroptosis Alleviates Acute Kidney Injury Associated with Severe Acute Pancreatitis in Rats |
| title_full | Inhibition of Caspase-11-Mediated Pyroptosis Alleviates Acute Kidney Injury Associated with Severe Acute Pancreatitis in Rats |
| title_fullStr | Inhibition of Caspase-11-Mediated Pyroptosis Alleviates Acute Kidney Injury Associated with Severe Acute Pancreatitis in Rats |
| title_full_unstemmed | Inhibition of Caspase-11-Mediated Pyroptosis Alleviates Acute Kidney Injury Associated with Severe Acute Pancreatitis in Rats |
| title_short | Inhibition of Caspase-11-Mediated Pyroptosis Alleviates Acute Kidney Injury Associated with Severe Acute Pancreatitis in Rats |
| title_sort | inhibition of caspase 11 mediated pyroptosis alleviates acute kidney injury associated with severe acute pancreatitis in rats |
| topic | caspase-11 pyroptosis severe acute pancreatitis acute kidney injury wedelolactone |
| url | http://dx.doi.org/10.1080/08941939.2022.2142868 |
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