RESUMO
Monosialoganglioside GM1 (GM1) has long been used as a therapeutic agent for neurological diseases in the clinical treatment of ischemic stroke. However, the mechanism underlying the neuroprotective function of GM1 is still obscure until now. In this study, we investigated the effects of GM1 in ischemia and reperfusion (I/R) brain injury models. Middle cerebral artery occlusion and reperfusion (MCAO/R) rats were treated with GM1 (60 mg·kg-1·d-1, tail vein injection) for 2 weeks. The results showed that GM1 substantially attenuated the MCAO/R-induced neurological dysfunction and inhibited the inflammatory responses and cell apoptosis in ischemic parietal cortex. We further revealed that GM1 inhibited the activation of NFκB/MAPK signaling pathway induced by MCAO/R injury. To explore its underlying mechanism of the neuroprotective effect, transcriptome sequencing was introduced to screen the differentially expressed genes (DEGs). By function enrichment and PPI network analyses, Sptbn1 was identified as a node gene in the network regulated by GM1 treatment. In the MCAO/R model of rats and oxygen-glucose deprivation and reperfusion (OGD/R) model of primary culture of rat cortical neurons, we first found that SPTBN1 was involved in the attenuation of I/R induced neuronal injury after GM1 administration. In SPTBN1-knockdown SH-SY5Y cells, the treatment with GM1 (20 µM) significantly increased SPTBN1 level. Moreover, OGD/R decreased SPTBN1 level in SPTBN1-overexpressed SH-SY5Y cells. These results indicated that GM1 might achieve its potent neuroprotective effects by regulating inflammatory response, cell apoptosis, and cytomembrane and cytoskeleton signals through SPTBN1. Therefore, SPTBN1 may be a potential target for the treatment of ischemic stroke.
Assuntos
Gangliosídeo G(M1) , Neurônios , Fármacos Neuroprotetores , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Transdução de Sinais , Animais , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Gangliosídeo G(M1)/farmacologia , Masculino , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/patologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Ratos , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Espectrina/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: Chlorhexidine (CH) and povidone-iodine (PI) are the most commonly used preoperative skin antiseptics at present. However, the prevention of the surgical site infection (SSI) and the incidence of skin adverse events do not reach a consistent statement and conclusion. This meta-analysis aimed to evaluate the efficacy of chlorhexidine and povidone-iodine in the prevention of postoperative surgical site infection and the incidence of corresponding skin adverse events. METHOD: Substantial studies related to "skin antiseptic" and "surgical site infection" were consulted on PUBMED, Web of Science, EMBASE, and CNKI. The primary outcome was the incidence of postoperative SSI. The secondary outcome was associated with skin adverse events. All data were analyzed with Revman 5.3 software. RESULTS: A total of 30 studies were included, including 29,006 participants. This study revealed that chlorhexidine was superior to povidone-iodine in the prevention of postoperative SSI (risk ratio [RR], 0.65; 95% confidence interval [CI], 0.55-0.77; p < 0.00001, I2 = 57%). Further subgroup analysis showed that chlorhexidine was superior to povidone-iodine in the prevention of postoperative SSI in clean surgery (risk ratio [RR], 0.81; 95% confidence interval [CI], 0.67-0.98; p = 0.03), I2 = 28%) and clean-contaminated surgery (risk ratio [RR], 0.58; 95% confidence interval [CI], 0.47-0.73; p < 0.00001, I2 = 43%). However, there was no statistically significant difference in the incidence of skin adverse events between CH and PI groups. CONCLUSION: Chlorhexidine was superior to povidone-iodine in preventing postoperative SSI, especially for the clean-contaminated surgery. However, there was no statistically significant difference in the incidence of skin adverse events between CH and PI groups.