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

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.