Empagliflozin Alleviates Renal Ischemia-Reperfusion Injury by Targeting AMPK/NLRP3 Signaling
Abstract
Background: Empagliflozin (EMPA), a sodium glucose cotransporter protein inhibitor, is a widely used hypoglycemic agent in clinical practice and possesses a protective effect against renal ischemia-reperfusion injury (RIRI); however, its underlying protective mechanism remains elusive. Activating NOD-like receptor protein 3 (NLRP3) inflammasome has a crucial influence in exacerbating the deterioration of renal function, and AMPK activation inhibits the activation of the NLRP3 inflammasome. Therefore, in this study, we aimed to ascertain whether EMPA protection against RIRI is achieved by targeting the adenylate-activated protein kinase (AMPK)/NLRP3 signaling pathway.
Methods: The RIRI model was established in mice by right nephrectomy and clipping the left renal artery for 60 minutes, immediately followed by 24 hours of reperfusion. The influence of EMPA on RIRI was assessed by measuring the content of BUN and creatinine, pathological kidney morphology, cell apoptosis, and the expression of AMPK, p-AMPK, caspase-1, NLRP3, ASC, MCP-1, TNF-α, IL-18, IL-1β, and IL-6.
Results: EMPA obviously inhibited the RIRI-induced kidney pathological injury and cell apoptosis; increased expression of BUN, creatinine, NLRP3, caspase-1, ASC, MCP-1, TNF-α, IL-18, IL-1β, and IL-6; and declined p-AMPK/AMPK. However, Compound C, an AMPK inhibitor, reduced the effects of EMPA in RIRI.
Conclusion: EMPA can effectively improve RIRI by inhibiting inflammation, and its mechanism may be closely…
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