Abstract：
OBJECTIVE: Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1), a component derived from medicinal plants, is known for its pharmacological benefits in IS, but its protective effects on BMECs have yet to be explored. This study aimed to investigate the potential protective effects of GRb1 on BMECs.
METHODS: An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools, including gene set enrichment analysis (GSEA), Gene Ontology (GO) classification and enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction network analysis, and molecular docking. Experimental validation was also performed to ensure the reliability of our findings.
RESULTS: Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically, GRb1 was found to modulate the interplay between oxidative stress, apoptosis, and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62), autophagy related 5 (ATG5), and hypoxia-inducible factor 1-alpha (HIF-1α) were identified, highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage.
CONCLUSIONS: GRbl protects BMECs against OGD/R injury by influencing oxidative stress, apoptosis, and autophagy. The identification of SQSTM1/p62, ATG5, and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS, providing a foundation for future research into its mechanisms and applications in IS treatment.
METHODS: An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools, including gene set enrichment analysis (GSEA), Gene Ontology (GO) classification and enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction network analysis, and molecular docking. Experimental validation was also performed to ensure the reliability of our findings.
RESULTS: Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically, GRb1 was found to modulate the interplay between oxidative stress, apoptosis, and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62), autophagy related 5 (ATG5), and hypoxia-inducible factor 1-alpha (HIF-1α) were identified, highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage.
CONCLUSIONS: GRbl protects BMECs against OGD/R injury by influencing oxidative stress, apoptosis, and autophagy. The identification of SQSTM1/p62, ATG5, and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS, providing a foundation for future research into its mechanisms and applications in IS treatment.
摘要：
目的：发现脑微血管内皮细胞（BMEC）在缺血性中风（IS）中从通常的非活动状态转变为活动状态，并引起神经元损伤。人参皂苷Rb1(GRb1),来自药用植物的成分，以其在IS中的药理益处而闻名，但其对BMECs的保护作用还有待探索。本研究旨在探讨GRb1对BMECs的潜在保护作用。
方法：建立体外氧糖剥夺/再灌注（OGD/R）模型，模拟缺血再灌注（I/R）损伤。使用人类自噬数据库和各种生物信息学工具分析大量RNA测序数据。包括基因集富集分析(GSEA)，基因本体(GO)分类和富集分析,京都基因和基因组百科全书（KEGG）途径分析，蛋白质-蛋白质相互作用网络分析，和分子对接。还进行了实验验证以确保我们的发现的可靠性。
结果：Rb1对受到OGD/R损伤的BMEC具有保护作用。具体来说,发现GRb1调节氧化应激之间的相互作用，凋亡，和自噬在BMEC中。关键目标，如隔离体1(SQSTM1/P62)，自噬相关5（ATG5），并鉴定了缺氧诱导因子1-α（HIF-1α），强调它们在介导GRb1对IS诱导损伤的保护作用中的潜在作用。
结论：GRbl通过影响氧化应激保护BMECs免受OGD/R损伤，凋亡，和自噬。SQSTM1/p62，ATG5和HIF-1α作为有希望的靶标的鉴定进一步支持了GRb1作为IS治疗剂的潜力。为未来研究其在IS治疗中的作用机制和应用奠定基础。
方法：建立体外氧糖剥夺/再灌注（OGD/R）模型，模拟缺血再灌注（I/R）损伤。使用人类自噬数据库和各种生物信息学工具分析大量RNA测序数据。包括基因集富集分析(GSEA)，基因本体(GO)分类和富集分析,京都基因和基因组百科全书（KEGG）途径分析，蛋白质-蛋白质相互作用网络分析，和分子对接。还进行了实验验证以确保我们的发现的可靠性。
结果：Rb1对受到OGD/R损伤的BMEC具有保护作用。具体来说,发现GRb1调节氧化应激之间的相互作用，凋亡，和自噬在BMEC中。关键目标，如隔离体1(SQSTM1/P62)，自噬相关5（ATG5），并鉴定了缺氧诱导因子1-α（HIF-1α），强调它们在介导GRb1对IS诱导损伤的保护作用中的潜在作用。
结论：GRbl通过影响氧化应激保护BMECs免受OGD/R损伤，凋亡，和自噬。SQSTM1/p62，ATG5和HIF-1α作为有希望的靶标的鉴定进一步支持了GRb1作为IS治疗剂的潜力。为未来研究其在IS治疗中的作用机制和应用奠定基础。
