【摘要】 目的：本研究主要目的是探讨人参皂苷Rb1是否通过G_s型G蛋白偶联受体（GPCR-G_s）发挥保护作用。方法：研究采用体外培养新生小鼠大脑原代星形胶质细胞，建立氧糖剥夺/复氧（OGD/R）细胞损伤模型。通过观察细胞形态，检测细胞活力、乳酸脱氢酶（LDH）释放、细胞凋亡率、细胞谷氨酸摄取率、脑源性神经营养因子（BDNF）含量，Rb1对星形胶质细胞存活及其标志性功能的影响，并对GPCR-G_s关联的信号分子环磷酸腺苷（cAMP）和蛋白激酶B(Akt）进行检测。结果：结果表明，Rb1在0.8-5μM浓度范围内对正常星形胶质细胞的活力、谷氨酸摄取和BDNF含量没有显著影响。但是在OGD/R状态下，Rb1可以显著改善星形胶质细胞活力，减少细胞LDH释放，降低细胞凋亡率。同时，Rb1能够显著提升OGD/R星形胶质细胞对谷氨酸的摄取能力，增加细胞内BDNF含量，提高OGD/R细胞内cAMP含量，激活Akt信号通路。当GPCR-G_s的G_s蛋白激活被抑制以后，Rb1对OGD/R损伤的星形胶质细胞的作用显著抑制。结论：以上研究结果提示，Rb1对OGD/R星形胶质细胞的保护作用，通过GPCR-G_s受体介导产生。本研究首次揭示人参皂苷Rb1对星形胶质细胞的保护作用的受体靶点，为进一步揭示Rb1作用的单个GPCR-G_s受体，阐明G_s受体与parthanatos的确切关系，奠定了坚实的研究基础。更多还原

【Abstract】 Objectives: To investigate whether the protective actions of ginsenoside Rb1(Rb1) on astrocytes are mediated through the G_s-type G-protein-coupled receptor(GPCR-G_s).Methods: Primary astrocyte cultures derived from neonatal mouse brain were used. Astrocyte injury was induced via oxygen-glucose deprivation/re-oxygenation(OGD/R). Cell morphology, viability, lactate dehydrogenase(LDH) leakage, apoptosis, glutamate uptake, and brain-derived neurotrophic factor(BDNF)secretion were assessed to gauge cell survival and functionality. Western blot was used to investigate the cyclic adenosine monophosphate(cAMP) and protein kinase B(Akt) signaling pathways. GPCR-G_s-specific inhibitors and molecular docking were used to identify target receptors.Results: Rb1 at concentrations ranging from 0.8 to 5 μM did not significantly affect the viability, glutamate uptake, or BDNF secretion in normal astrocytes. OGD/R reduced astrocyte viability, increasing their LDH leakage and apoptosis rate. It also decreased glutamate uptake and BDNF secretion by these cells. Rb1 had protective effects of astrocytes challenged by OGD/R, by improving viability, reducing apoptosis, and enhancing glutamate uptake and BDNF secretion. Additionally, Rb1 activated the c AMP and Akt pathways in these cells. When the GPCR-G_s inhibitor NF449 was introduced, the protective effects of Rb1 completely disappeared, and its activation of cAMP and Akt signaling pathways was significantly inhibited.Conclusion: Rb1 protects against astrocytes from OGD/R-induced injury through GPCR-G_s mediation.更多还原