右美托咪啶对缺氧缺血所致神经细胞损伤的影响及机制
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Effects and mechanism of dexmedetomidine on
neuronal cell injury induced by hypoxia-ischemia.
背景与目的
本研究旨在研究右美托咪定(DMED)对PC12与原代神经细胞缺氧缺糖(OGD)下所致缺氧缺血损伤的保护作用。
方 法
将PC12细胞暴露于OGD环境中以建立缺血模型。通过细胞活力的改变、凋亡和凋亡相关蛋白的表达来评价OGD诱导的细胞损伤程度。我们对OGD和DMED处理后氧化应激与神经营养因子的表达情况也进行了探索性观察。通过加入相关信号通路抑制剂，我们对OGD和DMED处理后可能涉及的信号通路的激活也进行了研究。最后根据炎症细胞因子释放和氧化应激的变化来证实DMED对原代神经元细胞的影响。
结 果
DMED能明显提高OGD处理后PC12细胞的活力、减少细胞凋亡并降低Bax/bcl-2比值。DMED处理可改善OGD引起的LDH、MDA、SOD、GSH-Px的变化及神经营养因子的降低。Notch/NF-κB信号通路中的关键激酶可被OGD上调，而DMED可降低此上调。此外，Notch或NF-κB抑制剂可增强DMED对OGD诱导的细胞损伤的影响。最终 DMED对原代神经细胞的保护作用得到了验证。
结 论
DMED对OGD-诱导的PC12细胞损伤具有保护作用，其机制可能与其抗凋亡、抗氧化活性及对Notch/NF-κB活化的抑制有关。我们的研究表明DMED可作为脑缺血的一种潜在治疗药物。
原始文献摘要
Liu Y J, Wang D Y, Yang Y J, et al. Effects and mechanism of dexmedetomidine on neuronal cell injury induced by hypoxia-ischemia[J]. Bmc Anesthesiology, 2017, 17(1):117.
Abstract.
BACKGROUND:
The present study aims to investigate the protective effects of dexmedetomidine (DMED) on hypoxia ischemia injury induced by oxygen and glucose deprivation (OGD) in PC12 and primary neuronal cells.
METHODS:
PC12 cells exposed to OGD was used to establish ischemia model. The OGD-induced cell injury was evaluated by alterations of cell viability, apoptosis and expressions of apoptosis-associated proteins. Oxidative stress and expressions of neurotrophic factors after OGD and DMED treatments were also explored. The activation of possible involved signaling pathways were studied after OGD and DMED treatments, along with the addition of inhibitors of these pathways. Finally, the effects of DMED on primary neuronal cells were verified according to the alterations of inflammatory cytokines release and oxidative stress.
RESULTS:
DMED obviously increased cell viability and reduced cell apoptosis as well as ratio of Bax/Bcl-2 in OGD-treated PC12 cells. Then, the OGD-induced changes of LDH, MDA, SOD and GSH-Px as well as decreases of neurotrophic factors were all ameliorated by DMED treatment. Key kinases in Notch/NF-κB signaling pathway were up-regulated by OGD, whereas the up-regulations were decreased by DMED. In addition, inhibitor of Notch or NF-κB could augment the effects of DMED on OGD-induced cell injury. Finally, the protective effects of DMED were verified in primary neuronal cells.
CONCLUSION:
DMED had protective effect on OGD-induced PC12 cell injury, depending on its anti-apoptotic, anti-oxidative activity and the inhibition of Notch/NF-κB activation. Our findings suggested that DMED could be used as a potential therapeutic drug for cerebral ischemia.
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