Abstract：
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.
摘要：
单唾液酸神经节苷脂GM1(GM1)在缺血性卒中的临床治疗中一直被用作神经系统疾病的治疗剂。然而,GM1神经保护功能的潜在机制至今仍不清楚。在这项研究中,我们研究了GM1在缺血再灌注(I/R)脑损伤模型中的作用.大脑中动脉闭塞再灌注（MCAO/R）大鼠接受GM1（60mg·kg-1·d-1，尾静脉注射）治疗2周。结果表明，GM1可以明显减轻MCAO/R诱导的缺血顶叶皮质的神经功能障碍，抑制炎症反应和细胞凋亡。我们进一步揭示了GM1抑制MCAO/R损伤诱导的NFκB/MAPK信号通路的激活。探讨其神经保护作用的潜在机制,引入转录组测序来筛选差异表达基因(DEGs)。通过功能丰富和PPI网络分析，Sptbn1被鉴定为由GM1处理调节的网络中的节点基因。在MCAO/R大鼠模型和氧糖剥夺再灌注(OGD/R)模型中原代培养大鼠皮层神经元,我们首先发现SPTBN1参与减轻GM1给药后I/R诱导的神经元损伤。在SPTBN1敲低SH-SY5Y细胞中，用GM1(20μM)处理显著增加SPTBN1水平。此外，OGD/R降低SPTBN1过表达SH-SY5Y细胞中SPTBN1的水平。这些结果表明，GM1可能通过调节炎症反应来实现其有效的神经保护作用。细胞凋亡，以及通过SPTBN1的细胞膜和细胞骨架信号。因此,SPTBN1可能是缺血性卒中治疗的潜在靶点。
