Hydrogen sulfide attenuates renal I/R‑induced activation of the inflammatory response and apoptosis via regulating Nrf2‑mediated NLRP3 signaling pathway inhibition

Su,Yonghong; Wang,Yaoqi; Liu,Min; Chen,Hongguang

doi:10.3892/mmr.2021.12157

Hydrogen sulfide attenuates renal I/R‑induced activation of the inflammatory response and apoptosis via regulating Nrf2‑mediated NLRP3 signaling pathway inhibition

Authors:
- Yonghong Su
- Yaoqi Wang
- Min Liu
- Hongguang Chen
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Affiliations: Department of Pediatric Surgery, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China, Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China, Department of Urinary Surgery, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China
Published online on: May 17, 2021 https://doi.org/10.3892/mmr.2021.12157
Article Number: 518
Copyright: © Su et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Renal ischemia/reperfusion (I/R) injury can lead to acute renal failure, delayed graft function and graft rejection. Nucleotide‑binding oligomerization domain NOD‑like receptor containing pyrin domain 3 (NLRP3)‑mediated inflammation participates in the development of renal injury. Nrf2 accelerates NLRP3 signaling pathway activation and further regulates the inflammatory response. In addition, hydrogen sulfide serves a protective role in renal injury; however, the detailed underlying mechanism remains poorly understood. The present study investigated whether Nrf2 and NLRP3 pathway participate in hydrogen sulfide‑regulated renal I/R‑induced activation of the inflammatory response and apoptosis. Wild‑type and Nrf2‑knockout (KO) mice underwent surgery to induce renal I/R via clamping of the bilateral renal pedicles. A total of 20 mg/kg MCC950 (an NLRP3 inhibitor) was injected intraperitoneally daily for 14 days prior to surgery. Renal tissue and blood were collected from the I/R model mice to analyze NLRP3 and Nrf2 mRNA expression levels, NLRP3, PYD and CARD domain containing, caspase‑1, IL‑1β, Nrf2 and heme oxygenase 1 protein expression levels, cell apoptosis, the secretion of tumor necrosis factor‑α, IL‑1β and IL‑6 cytokines and renal histopathology and function. Renal I/R activated the NLRP3 and Nrf2 signaling pathways. Conversely, MCC950 treatment inhibited activation of the NLRP3 signaling pathway, and prevented I/R‑induced renal injury, release of cytokines and apoptosis in renal I/R model mice. Sodium hydrosulfide (NaHS) not only alleviated upregulation of NLRP3 protein expression levels, but also relieved renal injury, release of cytokines and cell apoptosis induced by renal I/R in wild‑type mice, but not in Nrf2‑KO mice. NaHS alleviated NLRP3 inflammasome activation, renal injury, the inflammatory response and cell apoptosis via the Nrf2 signaling pathway in renal I/R model mice.

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