Sevoflurane inhibits neuronal apoptosis and expressions of HIF-1 and HSP70 in brain tissues of rats with cerebral ischemia/reperfusion injury.

Abstract

To observe the influences of sevoflurane on neuronal apoptosis and expressions of hypoxia-inducible factor 1 (HIF-1), and heat-shock protein 70 (HSP70) in brain tissues of rats with cerebral ischemia/reperfusion (I/R) injury. A total of 60 Sprague-Dawley rats were selected and divided into sham-operation group (Sham group, n=20), cerebral I/R model group (Model group, n=20), and 3% sevoflurane treatment group (Sevoflurane group, n=20). The rats in each group received neurological scoring, and the blood and brain tissues were collected to detect the concentrations of serum K+, Na+ and glucose (Glu). Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the levels of inflammatory factors [tumor necrosis factor-β (TNF-β) and interleukin-6 (IL-6)] and oxidative stress [catalase (CAT), malondialdehyde (MDA) and superoxide dismutase (SOD)]. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was performed to determine the nerve cell apoptosis in the brain tissues. The gene and protein expressions of Caspase-3, HIF-1, and HSP70 in the brain tissues were measured via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and Western blotting. In Sevoflurane group, the content of serum Glu and Na+ was decreased markedly, that of K+ was increased notably, and the levels of TNF-β, IL-1 and IL-6 were lowered remarkably compared with those in Model group (p<0.05). Moreover, the neurological score was reduced evidently (p<0.05). Model group had significantly strengthened the activity of MDA and CAT and decreased SOD content, while Sevoflurane group exhibited the opposite results. TUNEL staining showed that there were distinctly more apoptotic cells that were dominated by glial cells in Model group and fewer apoptotic cells in Sevoflurane group. It was indicated in gene assay that the messenger ribonucleic acid (mRNA) expression levels of HIF-1, HSP70, and Caspase-3 in Model group were remarkably higher than those in Sham group and Sevoflurane group (p<0.05). According to the results of Western blotting, the protein expressions of HIF-1 and HSP70 in Sevoflurane group were markedly lower than those in Model group. Sevoflurane can reduce the content of inflammatory factors, inhibit apoptosis, and reduce the expressions of HIF-1 and HSP70 in the case of cerebral I/R injury, thus exerting protective effects on rats with cerebral I/R injury.