Astragaloside IV Reduces Cerebral Ischemia/Reperfusion-Induced Blood-Brain Barrier Permeability in Rats by Inhibiting ER Stress-Mediated Apoptosis.
Astragaloside IV Reduces Cerebral Ischemia/Reperfusion-Induced Blood-Brain Barrier Permeability in Rats by Inhibiting ER Stress-Mediated Apoptosis.
复制标题
黄芪甲苷 IV 通过抑制 ER 应激介导的细胞凋亡来降低大鼠脑缺血/再灌注引起的血脑屏障通透性
DOI：
10.1155/2020/9087873
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Huang S
中科院分区：
文献类型：
--
作者：
Hou B;Liu R;Wu Y;Huang S
背景研究表明，AS-IV可抑制血脑屏障（BBB）通透性的增加。然而，其分子机制尚未阐明。本研究旨在探讨黄芪甲苷（AS-IV）对缺血再灌注后血脑屏障的保护作用及其机制。方法采用Long's五点评分法和氯化三苯基四氮唑（2，3，5-triphenyltetrazolium chloride）染色法，观察AS-IV对大鼠在体神经功能的保护作用。Evans蓝外渗法观察AS-IV对血脑屏障的保护作用。内质网应激和凋亡相关蛋白的水平通过蛋白质印迹法测定与AS-IV干预。采用western blot和流式细胞术检测细胞凋亡情况，western blot检测内质网应激相关蛋白水平。结果AS-IV能明显缩小脑缺血再灌注后大鼠脑梗死范围，并能明显保护BBB免受伊文思蓝的渗透。此外，发现缺血/再灌注或氧-葡萄糖剥夺/再灌注增加了内皮细胞凋亡蛋白，如Bax，Bcl-2和caspase-3，以及内质网应激相关蛋白，如磷酸化PERK和eIF 2 α，Bip和CHOP，这些蛋白通过AS-IV处理减弱。结论AS-IV可通过抑制内质网应激介导的内皮细胞凋亡，有效保护血脑屏障，缩小脑梗死面积。
Background Previous studies proved that AS-IV could prevent blood-brain barrier (BBB) against an increase in permeability. However, its underlying molecular mechanism has not been enlightened yet. The aim of the study is to reveal the potential protective mechanism of astragaloside IV (AS-IV) on the blood-brain barrier after ischemia-reperfusion. Methods In vivo, AS-IV neurological protection was measured by Long's five-point scale and 2,3,5-triphenyltetrazolium chloride staining. AS-IV protection for BBB was observed by Evans blue extravasation technique. Endoplasmic reticulum stress and apoptosis-related protein levels were measured by western blot with AS-IV intervention. In vitro, cell apoptosis was analyzed by western blot and flow cytometry.Endoplasmic reticulum stress-related protein levels were quantified through western blot. Results AS-IV treatment could decrease the infarct size in rats' brain and protect the BBB against Evans blue permeating through brain, after ischemia/reperfusion, significantly. Further, ischemia/reperfusion or oxygen‐glucose deprivation/reperfusion was found to have an increase in endothelial cell apoptosis proteins, such as Bax, Bcl-2, and caspase-3, and endoplasmic reticulum stress-associated proteins, such as phosphorylated PERK and eIF2α, Bip, and CHOP, which were attenuated by AS-IV treatment. Conclusions AS-IV can effectively protect the blood-brain barrier and reduce the area of cerebral infarction via inhibiting endoplasmic reticulum stress-mediated apoptosis in endothelial cells.