Effects of Ginsenoside Rb1 on Expressions of Phosphorylation Akt/Phosphorylation mTOR/Phosphorylation PTEN in Artificial Abnormal Hippocampal Microenvironment in Rats
Effects of Ginsenoside Rb1 on Expressions of Phosphorylation Akt/Phosphorylation mTOR/Phosphorylation PTEN in Artificial Abnormal Hippocampal Microenvironment in Rats
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DOI：
10.1007/s11064-018-2612-x
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发表时间：
2018-10-01
影响因子：
4.4
通讯作者：
Xian, Cory J.
中科院分区：
文献类型：
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作者：
Guo, Ying;Wang, Li-Ping;Xian, Cory J.
海马中l-谷氨酸（Glu）和Ca2+微灌注引起的人工异常微环境导致神经元损伤，这与脑缺血密切相关。人参皂苷Rb1是三七中的一种化合物，先前在微灌注模型中用于对抗人工异常海马环境。此外，虽然Akt/mTOR/PTEN信号通路在脑缺血中介导神经元保护，但该通路是否参与人参皂苷Rb1的神经保护尚不清楚。在这里，SH-SY5Y细胞暴露于OGD/R损伤，LY294002，人参皂苷Rb1，人参皂苷Rb1+LY294002。Western blotting检测磷酸化（P-）Akt/P- mtor /P- pten （OGD/R后24h）的表达。通过大鼠记忆功能（Morris水迷宫实验）、锥体细胞形态学变化（组织学）、海马中Akt、P- mtor和P- pten mRNA表达（qRT-PCR）和磷酸化（P-） （Western blotting和免疫组化染色）来检测其作用。人参皂苷Rb1可剂量依赖性地减轻Glu和Ca2+微灌注后大鼠的记忆缺陷和海马CA1区锥体细胞坏死和凋亡。Western blot结果显示，人参皂苷Rb1提高了体内外P-Akt、P-mTOR的表达，降低了P-PTEN的表达。因此，人参皂苷Rb1在人工异常微环境中的神经保护作用至少部分与激活P-AKT/P-mTOR信号通路和抑制P-PTEN蛋白有关。
Artificial abnormal microenvironment caused by microperfusion of l-glutamate (Glu) and Ca2+ in the hippocampus results in neuron damage, which is closely related to cerebral ischemia. Ginsenoside Rb1, a compound from Panax notoginseng, was previously used to counter the artificial abnormal hippocampal environment in a microperfusion model. In addition, while the Akt/mTOR/PTEN signaling pathway has been shown to mediate neuronprotection in cerebral ischemia, whether this pathway is involved in the neuroprotection of ginsenoside Rb1 is unknown. Here SH-SY5Y cells exposed to OGD/R injury in treated with LY294002, ginsenoside Rb1, ginsenoside Rb1+LY294002. Expressions of phosphorylation (P-)Akt/P-mTOR/P-PTEN (24h after OGD/R) were detected by Western blotting. Effects were examined via the memory function of rats (by Morris water maze test), morphological changes in pyramidal cell (by histology), and mRNA expression (by qRT-PCR) and phosphorylation (P-) (by Western blotting and immunohistochemical staining) of Akt, P-mTOR, and P-PTEN in the hippocampus. The memory deficit of rats and pyramidal cellular necrosis and apoptosis in the CA1 region of hippocampus after microperfusion of Glu and Ca2+ were dose dependently alleviated by ginsenoside Rb1.Moreover,Western blot showed that ginsenoside Rb1 increased the expressions of P-Akt, P-mTOR and reduced P-PTEN in vivo and vitro. Thus, the potent neuroprotection of ginsenoside Rb1 in artificial abnormal microenvironment is, at least partially, related to the activation of P-AKT/P-mTOR signaling pathway and inhibition of P-PTEN protein.