Astragaloside IV alleviates ischemia reperfusion-induced apoptosis by inhibiting the activation of key factors in death receptor pathway and mitochondrial pathway
Astragaloside IV alleviates ischemia reperfusion-induced apoptosis by inhibiting the activation of key factors in death receptor pathway and mitochondrial pathway
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DOI：
10.1016/j.jep.2019.112319
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发表时间：
2020-02-10
影响因子：
5.4
通讯作者：
Yang, Jiehong
中科院分区：
文献类型：
--
作者：
Yin, Fei;Zhou, Huifen;Yang, Jiehong
民族药理学相关性：细胞凋亡在脑缺血再灌注损伤中起重要作用，引发一系列病理改变，甚至可能危及生命。黄芪甲苷（Astragaloside-IV, AS-IV）是一种从黄芪（Astragalus aceus）中提取的天然化合物。邦吉。豆科植物（Leguminosae，黄芪）在脑缺血再灌注损伤研究中显示出神经保护作用。本研究探讨as - iv对大鼠短暂性脑缺血再灌注诱导的细胞凋亡的影响及其相关调控因子。方法：雄性SD大鼠术后一过性脑缺血再灌注给药AS-IV（12.5、25、50 mg/kg，每日1次，持续7 d）。连续给药7 d后，观察大鼠神经功能、脑梗死体积及脑组织病理变化。实时荧光定量PCR检测Fas、FasL、Caspase-8、Bax、Bcl-2 mRNA水平。western blot检测Caspase-8、Bid、Cytochrome C （Cyto C）、cleaved Caspase-3蛋白，免疫组织化学定量检测Cyto C。结果：AS-IV可显著减轻缺血再灌注损伤大鼠的神经功能缺损，减少脑梗死和神经元凋亡。AS-IV抑制Fas、FasL、Caspase-8和Bax/Bcl-2 mRNA的上调。此外，缺血再灌注后凋亡细胞因子Caspase-8、Bid、cleaved Caspase-3和Cyto C的蛋白水平也受到抑制，提示AS-IV可能通过抑制死亡受体通路和线粒体通路关键因子的激活来缓解缺血再灌注诱导的凋亡。
Ethnopharmacological relevance: Apoptosis plays an important role in cerebral ischemia-reperfusion injury and triggers a series of pathological changes which may even be life-threatening. Astragaloside-IV (AS-IV), a natural compound extracted from Astragalus (Astragalus membranaceus (Fisch.) Bunge., Leguminosae, Huangqi in Chinese), showed neuroprotective effects in the study of cerebral ischemia-reperfusion injury. In this study we investigate the effects of AS-IV on apoptosis induced by transient cerebral ischemia and reperfusion in rats, as well as the associated regulatory factors.Methods: AS-IV was administrated to male Sprague-Dawley (SD) rats after transient cerebral ischemia and reperfusion surgery (12.5, 25, and 50 mg/kg, once per day, continued for 7 days after surgey). After seven days of continuous administration, neurological function, cerebral infarction volume, and pathological changes of brain tissue were detected. Fas, FasL, Caspase-8, Bax, and Bcl-2 mRNA levels were determined by real-time PCR. Caspase-8, Bid, Cytochrome C (Cyto C), cleaved Caspase-3 proteins were determined by western blot and immunohistochemistry was used to quantify Cyto C.Results: AS-IV significantly attenuated the neurological deficit in rats with ischemica-reperfusion injury, and reduced cerebral infarction and neuronal apoptosis. AS-IV inhibited the mRNA upregulation of Fas, FasL, Caspase-8, and Bax/Bcl-2. Furthermore, the protein level of apoptosis cytokines Caspase-8, Bid, cleaved Caspase-3 and Cyto C were also inhibited after ischemia reperfusion, suggesting that AS-IV might alleviate ischemia reperfusion-induced apoptosis by inhibiting the activation of key factors in death receptor pathway and mitochondrial pathway.