Wang Yong, Ren Qianyao, Zhang Xing, Lu Huiling, Chen Jian
Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, China.
Department of Physiology, Guilin Medical University, Guilin, China.
Cell Physiol Biochem. 2018;45(2):537-546. doi: 10.1159/000487031. Epub 2018 Jan 25.
BACKGROUND/AIMS: Emerging evidence suggests that autophagy plays important roles in the pathophysiological processes of cerebral ischemia and reperfusion injury. Calycosin, an isoflavone phytoestrogen, possesses neuroprotective effects in cerebral ischemia and reperfusion in rats. Here, we investigated the neuroprotective effects of calycosin against ischemia and reperfusion injury, as well as related probable mechanisms behind autophagy pathways.
A cerebral ischemic and reperfusion injury model was established by middle cerebral artery occlusion in male Sprague-Dawley rats. Neurological scores, infarct volumes, and brain water content were assessed after 24 h reperfusion following 2 h ischemia. Additionally, the expression of the autophagy-related protein p62 and NBR1 (neighbor of BRCA1 gene 1), as well as Bcl-2, and TNF-α in rat brain tissues was measured by RT-PCR, western blotting and immunohistochemical analyses.
The results showed that calycosin pretreatment for 14 days markedly decreased infarct volume and brain edema, and ameliorated neurological scores in rats with focal cerebral ischemia and reperfusion. It was observed that levels of p62, NBR1 and Bcl-2 were greatly decreased, and levels of TNF-α significantly increased after ischemia and reperfusion injury. However, calycosin administration dramatically upregulated the expression of p62, NBR1 and Bcl-2, and downregulated the level of TNF-α.
All data reveal that calycosin exerts a neuroprotective effect on cerebral ischemia and reperfusion injury, and the mechanisms maybe associated with its anti-autophagic, anti-apoptotic and anti-inflammatory action.
背景/目的：新出现的证据表明，自噬在脑缺血再灌注损伤的病理生理过程中起重要作用。毛蕊异黄酮，一种异黄酮类植物雌激素，对大鼠脑缺血再灌注具有神经保护作用。在此，我们研究了毛蕊异黄酮对缺血再灌注损伤的神经保护作用以及自噬途径背后的相关可能机制。
通过大脑中动脉闭塞法在雄性Sprague-Dawley大鼠中建立脑缺血再灌注损伤模型。在缺血2小时后再灌注24小时后评估神经功能评分、梗死体积和脑含水量。此外，通过RT-PCR、蛋白质印迹和免疫组织化学分析测量大鼠脑组织中自噬相关蛋白p62和NBR1（BRCA1基因1的邻居）以及Bcl-2和TNF-α的表达。
结果表明，毛蕊异黄酮预处理14天可显著降低局灶性脑缺血再灌注大鼠的梗死体积和脑水肿，并改善神经功能评分。观察到缺血再灌注损伤后p62、NBR1和Bcl-2水平显著降低，TNF-α水平显著升高。然而，给予毛蕊异黄酮可显著上调p62、NBR1和Bcl-2的表达，并下调TNF-α水平。
所有数据表明，毛蕊异黄酮对脑缺血再灌注损伤具有神经保护作用，其机制可能与其抗自噬、抗凋亡和抗炎作用有关。
