Department of Neurosurgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, PR China.
Department of Neurology, Binzhou People's Hospital, Binzhou, Shandong Province, PR China.
Cell Biochem Biophys. 2021 Jun;79(2):301-310. doi: 10.1007/s12013-020-00965-8. Epub 2021 Jan 13.
The objective of this study is to investigate the roles of acteoside (ACT) in cells with oxygen-glucose deprivation and reoxygenation (OGD/R)-induced injury and the underlying mechanisms. The differentially expressed genes (DEGs) in rats with middle cerebral artery occlusion were identified using GSE61616 data set. Kyoto Encyclopedia of Genes and Genomes pathway enrichment with the DEGs and the prediction of ACT's targets were conducted using The Comparative Toxicogenomics Database. The OGD/R model was established with bEnd.3 cells. Following that, bEnd.3 cells were treated by distinct concentrations of ACT and IL-10. The proliferation and apoptosis of cells were analyzed by cell counting kit-8 and flow cytometry assays, respectively. Western blot was used to check involved proteins. Herein, we identified CCL2, CXCL10, and ICAM1 as the targets of ACT, which were upregulated in tissues of MACO rats and cells with OGD/R-induced injury. ACT promoted the proliferation but reduce the apoptosis of cells with OGD/R-induced injury. Moreover, these effects of ACT were enhanced by IL-10. After being treated with ACT, IL-10, or ACT together with IL-10, the levels of CCL2, CXCL10, and ICAM1 were all decreased, whereas p-Stat3 was raised in cells with OGD/R-induced injury, while Stat3 expression presented no significant difference among groups. ACT protected cells against OGD/R-induced injury through regulating the IL-10/Stat3 signaling, indicating that ACT might be an effective therapy drug to lower cerebral ischemia/reperfusion injury.
本研究旨在探讨毛蕊花糖苷（ACT）在氧葡萄糖剥夺和再氧合（OGD/R）诱导损伤细胞中的作用及其机制。使用 GSE61616 数据集鉴定大脑中动脉闭塞大鼠中的差异表达基因（DEGs）。使用比较毒理学基因组学数据库对 DEGs 进行京都基因与基因组百科全书通路富集分析和 ACT 靶标的预测。使用 bEnd.3 细胞建立 OGD/R 模型。随后，用不同浓度的 ACT 和 IL-10 处理 bEnd.3 细胞。通过细胞计数试剂盒-8 和流式细胞术分别分析细胞的增殖和凋亡。用 Western blot 检测相关蛋白。在此，我们确定 CCL2、CXCL10 和 ICAM1 为 ACT 的靶标，它们在 MACO 大鼠组织和 OGD/R 诱导损伤的细胞中上调。ACT 促进了 OGD/R 诱导损伤细胞的增殖，但减少了其凋亡。此外，IL-10 增强了 ACT 的这些作用。用 ACT、IL-10 或 ACT 与 IL-10 共同处理后，OGD/R 诱导损伤细胞中的 CCL2、CXCL10 和 ICAM1 水平均降低，而 p-Stat3 在 OGD/R 诱导损伤细胞中升高，而 Stat3 表达在各组间无显著差异。ACT 通过调节 IL-10/Stat3 信号通路保护细胞免受 OGD/R 诱导的损伤，表明 ACT 可能是一种降低脑缺血/再灌注损伤的有效治疗药物。
