人参皂苷Rg1对Aβ_(25-35)诱导的神经细胞核因子-κB活化的影响

目的探讨人参皂苷Rg1拮抗β淀粉样蛋白(Aβ)、保护神经细胞的作用是否与核因子κB(NF-κB)活化机制变化有关。方法分别以原代培养的大鼠海马神经元和星形胶质细胞为靶标建立Alzheimer病(AD)细胞模型。采用四唑盐显色(MTT)法检测细胞活力,进行Aβ25-35造模浓度、时间以及人参皂苷Rg1预处理最适宜浓度的选择。经Aβ25-35和Rg1干预后,用激光共聚焦显微镜检测分析FITC/PI双重标记的NF-κB在细胞内的激活程度,结合形态学观察分析人参皂苷Rg1对以上两种细胞的保护作用。结果40μmol.L-1的Aβ25-35作用24h后可激活原代培养星形胶质细胞的NF-κB(P<0.01),下调原代培养神经元的NF-κB活性(P<0.01)。2μmol.L-1的人参皂苷Rg1能明显提高神经元的NF-κB活性(P<0.01),减弱星形胶质细胞的NF-κB活性(P<0.01)。同时结合形态学观察和细胞活力检测发现,人参皂苷Rg1对两种细胞都有保护作用。结论人参皂苷Rg1通过启动神经元中NF-κB活化、下调星形胶质细胞的NF-κB活性,从两方面发挥其保护神经细胞的作用,从而有可能达到减缓AD发病进程的效果。

Effects of Ginsenoside Rg1 on the activation of NF-κB in neuronal cells induced by Aβ25-35

Aim To study the correlation between neuroprotection effect of ginsenoside Rg1 and the activation of nuclear factor kappa B (NF-κB) in neuronal cells induced by β-amyloid peptide 25-35 (Aβ25-35).Methods Rat astrocyte and hippocampal neuron cell models of Alzheimers disease (AD) were induced by Aβ25-35, respectively. The optimal concentration and duration of Aβ25-35 for cell models of AD and the optimal concentration and duration of Rg1 for pretreatment were determined according to cellular morphology and MTT colorimetric analysis. The activity of NF-κB in two kinds of cells was analyzed by laser scanning confocal microscope (LSCM) with double marked by FITC/PI. Results Aβ25-35(40 μmol·L-1for 24 h) was selected as the stable effective concentration and time point to make cell models of AD in neurons and astrocytes. 40 μmol·L-1 of Aβ25-35 up-regulates the activity of NF-κB (P<0.01) in astrocytes and down-regulates the activity of NF-κB in neurons(P<0.01). 2 μmol·L-1 of Ginsenoside Rg1 protects neurons through switching on the activation of NF-κB (P<0.01), and protects astrocytes through inhibiting the degree of activation NF-κB (P<0.01).Conclusion Ginsenoside Rg1 protects neurons through down-regulating the activity of NF-κB in astrocytes and up-regulating the activity of NF-κB in neurons. These results give new evidence and mechanism that Ginsenoside Rg1 has therapeutic benefits in AD.