Effects of edaravone combined with Oxiracetam on neuronal apoptosis in rats with cerebral infarction through targeting SIRT1/NF-κB inflammatory pathway.

Abstract

The objective of this study was to investigate the effects of edaravone combined with oxiracetam on neuronal apoptosis in rats with cerebral infarction (CI) and to explore the potential molecular mechanism. A total of 36 Sprague-Dawley rats were randomly divided into sham-operation group (n=12), model group (n=12) and treatment group (n=12). Only the external carotid artery was exposed in sham-operation group, while the models of CI were established using suture method in the other two groups. After modeling, the rats in sham-operation group and model group were intraperitoneally injected with normal saline, and those in treatment group were administered with edaravone and oxiracetam solutions via intraperitoneal injection. Then, the specimens were obtained at 2 weeks after intervention. The cognitive function of the rats was evaluated using a water maze, Nissl staining was applied to observe the neuronal morphology, and the relative protein expressions of silent information regulator 1 (SIRT1) and NF-κB were measured by means of Western blotting. Furthermore, quantitative polymerase chain reaction (qPCR) was performed to determine the messenger ribonucleic acid (mRNA) expressions of interleukin-1 beta (IL-1β) and IL-6, the content of IL-1β and IL-6 was detected by enzyme-linked immunosorbent assay (ELISA), and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was conducted to examine the cell apoptosis. Model group displayed a significantly longer escape latency and significantly fewer times of crossing the original platform than sham-operation group (p<0.05), whereas treatment group had a significantly shorter escape latency but significantly more times of crossing the original platform than model group (p<0.05). The relative protein expression level of SIRT1 was lowered significantly, while that of NF-κB was elevated significantly in model group in comparison with those in sham-operation group (p<0.05), and the opposite results were observed between model group and treatment group (p<0.05). Besides, the content of IL-1β and IL-6 in brain tissues was increased significantly in model group compared with that in sham-operation group (p<0.05), but it was decreased significantly in treatment group in comparison with that in model group (p<0.05). The relative mRNA expression levels of IL-1β and IL-6 were significantly higher in model group than those in sham-operation group (p<0.05). Moreover, model group exhibited more positive apoptotic cells and a significantly higher apoptosis rate than sham-operation group (p<0.05) and treatment group (p<0.05). No apparent abnormalities of neuronal morphology and structure were detected in sham-operation group, with many Nissl bodies. The neurons were damaged, with abnormal morphology and structure, and there were a small number of Nissl bodies in model group. The neurons were damaged in treatment group, but their morphology and structure were improved evidently compared with those in model group. Edaravone combined with oxiracetam can inhibit the neuronal apoptosis in CI rats by regulating the SIRT1/NF-κB signaling pathway, thereby exerting a neuroprotective effect.