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MEK/ERK 通路介导丹酚酸 B 对氧化应激诱导的大鼠骨髓基质干细胞凋亡的保护作用。

MEK/ERK pathway mediates cytoprotection of salvianolic acid B against oxidative stress-induced apoptosis in rat bone marrow stem cells.

机构信息

Department of Pathophysiology, Sun YatSen University, Guangzhou, Peoples Republic of China.

出版信息

Cell Biol Int. 2010 Nov;34(11):1063-8. doi: 10.1042/CBI20090126.

DOI:10.1042/CBI20090126
PMID:20629637
Abstract

To improve the survival and/or differentiation of grafted BMSCs (bone marrow stem cells) represents one of the challenges for the promising cell-based therapy. Considerable reports have implicated Sal B (salvianolic acid B), a potent aqueous extract of Salvia miltiorrhiza, in enhancing the survival of cells under various conditions. In this study, we investigated the effect of Sal B on H₂O₂-induced apoptosis in rat BMSCs, focusing on the survival signalling pathways. Results indicated that the MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase] inhibitor (PD98059) and 10 μM Sal B remarkably prevented BMSCs from H₂O₂-induced apoptosis through attenuating caspase-3 activation, which is accompanied by the significant up-regulation of Bcl-2. In addition, the ROS (reactive oxygen species) accumulation was also reduced after Sal B treatment. Furthermore, Sal B inhibited the ERK1/2 phosphorylations stimulated by H₂O₂. Taken together, our results showed that H₂O₂-induced apoptosis in BMSCs via the ROS/MEK/ERK1/2 pathway and Sal B may exert its cytoprotection through mediating the pathway.

摘要

提高移植骨髓间充质干细胞(BMSCs)的存活率和/或分化率是细胞治疗有前途的方向之一。有大量报道表明,丹参中的有效水溶性成分丹参素 B(Sal B)在各种条件下增强细胞存活率方面具有重要作用。在这项研究中,我们研究了 Sal B 对 H₂O₂诱导的大鼠 BMSCs 凋亡的影响,重点研究了存活信号通路。结果表明,MEK [丝裂原活化蛋白激酶/细胞外信号调节激酶(ERK)激酶]抑制剂(PD98059)和 10 μM Sal B 通过减弱半胱天冬酶-3 的激活,显著阻止 BMSCs 发生 H₂O₂诱导的细胞凋亡,Bcl-2 的表达显著上调。此外,Sal B 处理后 ROS(活性氧)的积累也减少了。此外,Sal B 抑制了 H₂O₂刺激的 ERK1/2 磷酸化。总之,我们的研究结果表明,H₂O₂通过 ROS/MEK/ERK1/2 通路诱导 BMSCs 凋亡,Sal B 可能通过介导该通路发挥其细胞保护作用。

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