Aralia taibaiensis Protects against I/R-Induced Brain Cell Injury through the Akt/SIRT1/FOXO3a Pathway
Aralia taibaiensis Protects against I/R-Induced Brain Cell Injury through the Akt/SIRT1/FOXO3a Pathway
复制标题
太白楤木通过 Akt/SIRT1/FOXO3a 通路预防缺血再灌注引起的脑细胞损伤
DOI：
10.1155/2019/7609765
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发表时间：
2019-01-01
影响因子：
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通讯作者：
Qiao, Boling
中科院分区：
文献类型：
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作者：
Duan, Jialin;Cui, Jia;Qiao, Boling
研究背景太白木皂苷（Saponin from Aralia taibaiensis，sAT）在多种模型中显示出良好的抗氧化作用，但其对脑细胞的影响尚不清楚。本研究旨在探讨sAT对缺血/再灌注损伤的保护作用及其机制。方法体外培养HT 22细胞，用sAT预处理后，再进行I/R。测定细胞凋亡率、线粒体功能和抗氧化蛋白。为了阐明机制，使用siRNA。在体内，通过灌胃给予sAT预处理7天，并诱导I/R模型。测定神经行为学评分、脑梗死体积及脑组织细胞因子。通过Western印迹法研究蛋白质水平。结果sAT对缺血再灌注引起的细胞凋亡和线粒体功能障碍有明显的保护作用。抗氧化蛋白水平以剂量依赖性方式增加。进一步研究发现sAT可诱导PGC-1α和FOXO 3a的脱乙酰化和磷酸化。sAT处理还诱导Akt的磷酸化水平和SIRT 1的表达水平。利用特异性靶向siRNA转染，验证了Akt、SIRT 1、PGC-1α和FOXO 3a之间的相互关系。此外，在I/R大鼠中也观察到相同的保护作用。结论sAT通过调节Akt/SIRT 1/FOXO 3a/PGC-1α信号通路保护脑细胞免受缺血再灌注损伤。
Background Saponin from Aralia taibaiensis (sAT) showed excellent antioxidative effects in several models; however, its effects on brain cells were unknown to us. The present study was designed to evaluate the protective effects of sAT on ischemia/reperfusion- (I/R-) induced injury and clarify its mechanisms. Methods In vitro, HT22 cells were pretreated with sAT and then subjected to I/R. Apoptosis rate, mitochondrial function, and antioxidant proteins were measured. To clarify the mechanisms, siRNA were used. In vivo, sAT was pretreated through intragastric administration for 7 days and the I/R model was induced. The neurobehavioral scores, infarction volumes, and some cytokines in the brain were measured. Protein levels were investigated by Western blotting. Results The results showed that sAT treatment significantly protected cells from I/R-induced cell apoptosis and mitochondrial dysfunction. The antioxidant protein levels were increased in a dose-dependent manner. Further study revealed that sAT induced the deacetylation and phosphorylation of PGC-1α and FOXO3a. sAT treatment also induced the phosphorylation levels of Akt and the expression levels of SIRT1. Using the specific targeted siRNA transfection, the interplay relationship between Akt, SIRT1, PGC-1α, and FOXO3a was verified. Furthermore, the same protective effects were also observed in rats subjected to I/R. Conclusion sAT protected brain cells from I/R-induced mitochondrial oxidative stress and dysfunction through regulating the Akt/SIRT1/FOXO3a/PGC-1α pathway.