Tetramethylpyrazine Protects Bone Marrow-Derived Mesenchymal Stem Cells against Hydrogen Peroxide-Induced Apoptosis through PI3K/Akt and ERK1/2 Pathways
Tetramethylpyrazine Protects Bone Marrow-Derived Mesenchymal Stem Cells against Hydrogen Peroxide-Induced Apoptosis through PI3K/Akt and ERK1/2 Pathways
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DOI：
10.1248/bpb.b17-00524
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发表时间：
2017-12-01
影响因子：
2
通讯作者：
Zhang, Jianping
中科院分区：
文献类型：
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作者：
Fang, Yan;Chu, Lisheng;Zhang, Jianping
骨髓间充质干细胞移植是治疗缺血性脑卒中的新策略之一。然而，移植的骨髓间充质干细胞在缺血组织中的低存活率限制了这种方法的治疗效果。氧化应激是脑缺血的主要发病机制，对移植的BMSCs的存活有负面影响。川芎嗪（TMP）具有很强的抗氧化活性。本研究旨在观察川芎嗪预处理对过氧化氢（H2O2）诱导的BMSCs凋亡的保护作用，并探讨川芎嗪预处理抗BMSCs凋亡的可能机制。用TMP（10、25、50、100、200 μ mol/L）预处理骨髓基质细胞24 h，然后用500 μ mol/L的H2O2处理24 h。我们发现，TMP预处理显着增加细胞活力，减少细胞凋亡和细胞内活性氧（ROS）的产生。TMP的保护作用与Bcl-2表达增加、Bax表达减弱、磷酸化Akt（p-Akt）和细胞外调节蛋白激酶1/2（p-ERK 1/2）水平升高有关。进一步的研究发现，TMP的这些有益作用被Wortmannin（磷酸肌醇-3激酶（PI3K）抑制剂）或PD98059（ERK 1/2抑制剂）显著阻断。总之，我们的研究结果证实，TMP通过调节PI3K/Akt和ERK 1/2信号通路保护BMSCs免受H2O2诱导的凋亡，这表明TMP可与BMSCs联合使用以改善细胞存活用于治疗缺血性卒中。
Bone marrow-derived mesenchymal stem cells (BMSCs) transplantation is one of the new therapeutic strategies for treating ischemic stroke. However, the poor survival rate of transplanted BMSCs in ischemic tissue limits the therapeutic efficacy of this approach. Oxidative stress is a major mechanism underlying the pathogenesis of brain ischemia and has a negative impact on the survival of transplanted BMSCs. Tetramethylpyrazine (TMP) has been reported to possess potent antioxidant activity. In the present study, we aimed to investigate the protective effects of TMP pretreatment on BMSCs survival of hydrogen peroxide (H2O2)-induced apoptosis in vitro and to elucidate the potential antiapoptotic mechanisms of TMP pretreatment on BMSCs. BMSCs were pretreated with TMP (10, 25, 50, 100, and 200 mu mol/L) for 24h and then exposed to 500 mu mol/L of H2O2 for 24h. We found that TMP pretreatment significantly increased cell viability and decreased cell apoptosis and intracellular reactive oxygen species (ROS) generation. Furthermore, the protective effects of TMP were related to increased Bcl-2 expression, attenuated Bax expression, and enhanced levels of phosphorylated Akt (p-Akt) and extracellular regulated protein kinases1/2 (p-ERK1/2). Further studies found that these beneficial effects of TMP were significantly blocked by wortmannin (an inhibitor of phosphoinositide-3 kinase (PI3K)) or PD98059 (an inhibitor of ERK1/2). In conclusion, our results confirm that TMP protects BMSCs against H2O2-induced apoptosis by regulating the PI3K/Akt and ERK1/2 signaling pathways, suggesting that TMP may be used in combination with BMSCs to improve cell survival for the treatment of ischemic stroke.