Osthole Protects Bone Marrow-Derived Neural Stem Cells from Oxidative Damage through PI3K/Akt-1 Pathway
Osthole Protects Bone Marrow-Derived Neural Stem Cells from Oxidative Damage through PI3K/Akt-1 Pathway
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DOI：
10.1007/s11064-016-2082-y
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发表时间：
2017-02-01
影响因子：
4.4
通讯作者：
Yang, Jing-xian
中科院分区：
文献类型：
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作者：
Yan, Yu-hui;Li, Shao-heng;Yang, Jing-xian
近年来，神经干细胞移植作为治疗神经退行性疾病的一种方法得到了广泛的探索。神经干细胞是一种特殊的细胞，具有一定的自我更新能力和分化为多种细胞类型的潜力。然而，病变组织的炎症环境不利于移植细胞的存活。蛇床子素(Ost)是蛇床子、当归等中药的主要活性成分。OST具有广泛的药理活性，如抗炎、免疫调节、神经保护等。在本研究中，我们评价了OST对骨髓源性神经干细胞(BM-NSCs)对抗过氧化氢(H_2O_2)损伤的保护作用。BM-NSCs分别用不同剂量的OST和H_2O_2处理。细胞计数试剂盒-8(CCK-8)法和乳酸脱氢酶(LDH)漏出法测定细胞活力。采用原位末端标记法(TUNEL)和逆转录聚合酶链式反应(RT-PCR)检测OST对细胞凋亡的影响。结果表明，Ost对H_2O_2诱导的细胞损伤具有保护作用，与H_2O_2组相比，Ost预处理组的细胞凋亡率明显减少。Bax/Bc l-2m RNA表达比值也降低。Western blotting分析了PI3K/Akt-1信号通路相关蛋白的表达水平，结果表明OST可增加p-Akt和PI3K的表达。提示Ost对BM-NSCs具有保护作用，可改善神经退行性疾病的炎症环境，提高移植NSCs的存活率。
In recent years, neural stem cell (NSC) transplantation has been widely explored as a treatment for neurodegenerative diseases. NSCs are special cells that have some capacity for self-renewal and the potential to differentiate into multiple cell types. However, the inflammatory environment of diseased tissue is not conducive to the survival of transplanted cells. Osthole (Ost) is a principal bioactive component of Fructus Cnidii, Radix Angelicae Pubescentis and other traditional Chinese medicines. Ost has a wide range of pharmacological activities, such as anti-inflammation, immunomodulation, and neuroprotection. In the present study, we assessed the protective effects of Ost on bone marrow-derived-NSCs (BM-NSCs) against injury induced by hydrogen peroxide (H2O2). BM-NSCs were pre-treated with different doses of Ost and treated with H2O2. The cell counting kit-8 (CCK-8) method and lactate dehydrogenase (LDH) leakage assay were used to determine cell viability. Using the TUNEL assay and RT-PCR, we evaluated the effect of Ost on cell apoptosis. The results showed that Ost had protective effects against H2O2-induced cell damage, and the number of apoptotic cells was significantly decreased in the Ost pre-treated groups compared to the H2O2 group. The expression ratio of Bax/Bcl-2 mRNA was also decreased. Furthermore, western blotting was used to analyze levels of proteins related to PI3K/Akt-1 signaling pathway, and results indicated that ost can increase p-Akt and PI3K. Our findings suggested that Ost protects BM-NSCs against oxidative stress injury, and it can be used to improve the inflammatory environment of neurodegenerative diseases so and promote the survival rate of transplanted NSCs.