TY -的A2 - Tu, Wen-Jun盟,赵小勇非盟-李,掸族盟- Mo, Yunchang AU - Li Ruru盟——黄Shaoyi盟——张Anqi AU - Ni Xuqing盟——戴Qinxue AU -王,Junlu PY - 2021 DA - 2021/10/19 TI - DCA抵御氧化损伤归因于大脑缺血再灌注通过调节糖酵解PDK2-PDH-Nrf2轴SP - 5173035六世- 2021 AB -脑缺血性中风(是)仍然是一个困难的问题需要解决;能量代谢衰竭是主要因素导致线粒体功能障碍和氧化应激损伤在脑缺血的发病机制,产生大量的活性氧(ROS)并打开血脑屏障。二氯乙酸(DCA)可以抑制丙酮酸脱氢酶激酶(此后)。此外,DCA表明了增加线粒体丙酮酸吸收的能力,促进氧化葡萄糖的糖酵解过程中,从而提高丙酮酸脱氢酶的活性(PDH)。因此,丙酮酸流提升为三羧酸循环加快的ATP生产。DCA有保护作用和脑缺血/再灌注(I / R)损伤,但具体机制尚不清楚。本研究采用一个短暂性大脑中动脉闭塞(MCAO)小鼠模型模拟和I / R损伤的老鼠。我们调查了DCA的机制调节糖酵解和保护I / R损伤引起的氧化损伤通过PDK2-PDH-Nrf2轴。从这项研究的结果表明,DCA可以改善糖酵解,减少氧化应激和神经元死亡,破坏血脑屏障,促进氧化代谢的恢复通过抑制PDK2和激活PDH。此外,DCA明显提高神经系统评分,减少梗塞体积,脑含水量,坏死的神经元。 Moreover, as suggested from the results, DCA elevated the content of Nrf2 as well as HO-1, i.e., the downstream antioxidant proteins pertaining to Nrf2, while decreasing the damage of BBB and the degradation of tight junction proteins. To simulate the condition of hypoxia and ischemia in vitro, HBMEC cells received exposure to transient oxygen and glucose deprivation (OGD). The DCA treatment is capable of reducing the oxidative stress and blood-brain barrier of HBMEC cells after in vitro hypoxia and reperfusion (H/R). Furthermore, this study evidenced that HBMEC cells could exhibit higher susceptibility to H/R-induced oxidative stress after ML385 application, the specific inhibitor of Nrf2. Besides, the protection mediated by DCA disappeared after ML385 application. To sum up, as revealed from the mentioned results, DCA could exert the neuroprotective effect on oxidative stress and blood-brain barrier after brain I/R injury via PDK2-PDH-Nrf2 pathway activation. Accordingly, the PDK2-PDH-Nrf2 pathway may play a key role and provide a new pharmacology target in cerebral IS and I/R protection by DCA. SN - 1942-0900 UR - https://doi.org/10.1155/2021/5173035 DO - 10.1155/2021/5173035 JF - Oxidative Medicine and Cellular Longevity PB - Hindawi KW - ER -