Salidroside alleviates ischemic brain injury in mice with ischemic stroke through regulating BDNK mediated PI3K/Akt pathway
Salidroside alleviates ischemic brain injury in mice with ischemic stroke through regulating BDNK mediated PI3K/Akt pathway
复制标题
红景天苷通过调节 BDNK 介导的 PI3K/Akt 通路减轻缺血性脑卒中小鼠缺血性脑损伤
DOI：
10.1016/j.bcp.2018.08.015
复制
发表时间：
2018-10-01
影响因子：
5.8
通讯作者：
Liu, Chao
中科院分区：
文献类型：
--
作者：
Zhang, Xu;Du, Qianming;Liu, Chao
有证据表明，抑制细胞凋亡在防止脑缺血/再灌流后神经元损伤甚至死亡方面起着至关重要的作用，这为临床治疗脑损伤显示了潜在的治疗潜力。本研究分别建立了C57BL/6J野生型(BDNK+/+)和BDNK基因敲除(BDNF-/-)小鼠MCAO模型，并探讨了红景天苷的神经保护作用及其机制。结果表明，丹参能显著逆转脑梗塞面积，减轻脑水肿，降低神经功能缺损评分，减少TUNEL阳性细胞数。但BDNK缺乏抑制了SAL的神经保护作用。此外，丹参还可通过降低LDH活性，提高细胞存活率，减轻神经细胞损伤，抑制细胞凋亡率。SAL通过DNA结合依赖性和非依赖性机制抑制细胞凋亡。PI3K基因敲除小鼠(PI3K-/-)和siRNA-PI3K对BDNK的保护作用是通过PI3K/Akt途径实现的。综上所述，SAL可通过DNA结合依赖和非依赖的方式调节BDNK介导的PI3K/Akt凋亡通路，从而成为脑I/R损伤后有效的神经保护剂。
There is evidence suggesting that inhibition of apoptosis plays a critical role in preventing neurons from damage and even death, after brain ischemia/reperfusion, which shows therapeutic potential for clinical treatment of brain injury. In this study, We preformed MCAO model in C57BL/6J wild-type (BDNK +/+) and BDNK knockout (BDNF -/-) mice respectively, and investigated the neuroprotective effect of Salidroside (Sal) and its underlying mechanisms. The results showed that Sal reversed brain infarct size, reduced cerebral edema, decreased the neurological deficit score and diminished TUNEL positive cells significantly. However, BDNK deficiency inhibited the neuroprotective effect of Sal. In addition, Sal increased cell viability, ameliorated neuron cell injury by decreasing LDH activity, and inhibited cell apoptotic rate. Sal suppressed apoptotic signaling via DNA binding-dependent and-independent mechanisms. Furthermore, the neuroprotective effect of Sal on BDNK was mediated by PI3K/Akt pathway, which was proved by the use of PI3K knockout (PI3K -/-) mice and siRNA-PI3K. In summary, these data strongly suggested that Sal could be used as an effective neuroprotective agent to protect against ischemic stroke after cerebral I/R injury through regulating BDNK-mediated PI3K/Akt apoptotic pathway in DNA-binding-dependent and -independent manners.