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Sevoflurane improves renal ischemia-reperfusion injury in rats through RISK signaling pathway
Abstract
Purpose: To investigate the effect of sevoflurane on renal ischemia-reperfusion injury (IRI) in rats and its regulatory effect on reperfusion injury salvage kinase (RISK) signaling pathway.
Methods: A total of thirty (30) Sprague-Dawley rats were randomly divided into sham, model and sevoflurane groups with 10 animals per group. Renal IRI models were created in model and sevoflurane groups, while sham group had no ligation. Renal injury was determined using hematoxylin and eosin (HE) staining. Blood urea nitrogen (BUN) and serum creatinine (Scr) levels were assayed while apoptosis was determined via terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. Enzyme-linked immunosorbent assay (ELISA) was used to assess malonaldehyde (MDA) content and inflammatory factors in kidney tissues and peripheral blood, respectively. Reactive oxygen species (ROS) level was determined using 2,7-dichlorodi-hydro fluorescein diacetate (DCFHDA) while Western blotting was used to determine the expression of apoptosis- and RISK signaling pathway-related proteins in kidney tissues.
Results: Compared to model group, renal injury in sevoflurane group rats was significantly alleviated (p < 0.01). The levels of BUN and Scr in peripheral blood, apoptosis level in kidney tissues, MDA content and ROS level in kidney tissues, interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 content, and content of caspase-3 protein in kidney tissues were significantly reduced (p < 0.01), whereas IL-10 content, Bcl-2/Bax ratio and expression levels of p-ERK1/2, p-Akt and phosphorylated glycogen synthase kinase 3β (p-GSK-3β) were significantly increased (p < 0.01) in the sevoflurane group.
Conclusion: Sevoflurane represses the release of inflammatory factors, lowers ROS level and apoptosis of renal cells and improves renal function through activation of RISK signaling pathway in kidney tissues of rats with renal IRI. Thus, sevoflurane is a potential agent for the treatment of IRI.