中文摘要：

目的探讨人参皂苷（ginsenoside，GS）对蛋白磷酸酶抑制剂冈田酸（OA）诱导拟Alzheimer病（AD）细胞模型神经细胞tau蛋白的磷酸化、微管、细胞凋亡和凋亡调节因子的影响。方法GS与人神经母细胞瘤细胞系SK-N-SH细胞预孵育24h，弃去培养基，然后用OA 10 nmol·L^-1与SK-N-SH细胞共孵育6h；用倒置显微镜观察细胞形态的变化，激光共聚焦显微镜观察微管变化，Western blot方法观察磷酸化tau蛋白、凋亡因子Bcl-2、Bax和Caspase-3的表达，用TUNEL法观察凋亡细胞的变化。结果正常SK-N-SH神经细胞铺展良好，OA模型组细胞突起断裂，GS显示了细胞保护作用。通过激光共聚焦显微镜观察，正常SK-N-SH细胞微管粗壮、连续，而OA模型组微管断裂、消失；GS能够减少OA引起的微管破坏作用。OA模型组tau蛋白Ser-199／202和Ser-404位点磷酸化水平较正常对照组明显增高，非磷酸化水平较正常对照组明显下降；GS50 mg·L^-1和100 mg·L^-1组使神经细胞tau蛋白Ser-199／202和Ser-404位点磷酸化水平较OA模型组明显下降，GS50 mg·L^-1和100 mg·L^-1组的tau蛋白Ser202非磷酸化水平较模型组则明显升高；正常对照组未见凋亡细胞；OA模型组凋亡细胞明显增多，Bax和Caspase-3表达水平较正常对照组明显增高，Bcl-2水平明显下降；GS能够明显抑制OA诱导的细胞凋亡，减少Bax和Caspase-3表达。结论人参皂苷对蛋白磷酸酶抑制剂OA所致的神经细胞病理变化有明显的保护作用，可能是通过抑制tau蛋白过度磷酸化，防止细胞凋亡来发挥作用的，提示该药在防治AD方面可能具有良好的应用前景。

英文摘要：

Aim To investigate the effects of ginsenoside （GS） on phosphorylation of tau protein, microtu- bule, cellular apoptosis and its related factors in cellular model of Alzheimer disease （AD） induced by the protein phosphatase 1 and 2A inhibitor okadaic acid （OA）. Methods The human neuroblastoma cell line SK-N-SH cells were cultured with GS for 24 h, the culture medium was changed, and then incubated with OA 10 nmol·L^-1 for 6 h. The changes of cell morphology were observed by inverted microscope. The laser confocal microscopy was used to observe the microtubule changes. Western blot was applied to determine the expression of phosphorylation of tau protein, and apoptosis-regulating factors Bcl-2, Bax and Caspase-3. The changes of apoptotic cells were observed by TUNEL method. Results The normal SK-N-SH cells spread well. OA-treated cells showed that the cell axons and the microtubules were broken and decreased under the inverted microscope and laser confocal microscope. Preincubation of GS demonstrated the significantly protective effects against the morphologic damage induced by OA. In OA-treated group, the phosphorylation of tau protein at Ser-199/202 and Ser-404 sites was higher than that in normal group, and the non-phosphorylation of tau protein at the same sites was lower; Incubation of GS at the dose of 50 mg·L^-1 and 100 mg·L^-1 with the cells decreased the phosphorylation of tau protein Ser-199/202 and Ser-404 sites. GS group at the dose of 50 mg·L^-1 and 100 mg·L^-1 decreased the expression of at non-phosphorylation of tau protein at the Ser202 site. The apoptotic cells were not found in normal group. The number of apoptotic cells were obviously increased, the expression of Bax and caspase-3 significantly enhanced, and Bcl-2 expression decreased in the OA-treated model group. GS significantly decreased the apoptotic cell number of nerve cells, inhibited the expression of Bax and caspase-3. Conclusion GS can protect the nerve cells from pathological change induced by OA. Maybe because it can