Resveratrol attenuates brain damage in permanent focal cerebral ischemia via activation of PI3K/Akt signaling pathway in rats
Resveratrol attenuates brain damage in permanent focal cerebral ischemia via activation of PI3K/Akt signaling pathway in rats
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DOI：
10.1080/01616412.2018.1509826
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发表时间：
2018-12-02
影响因子：
1.9
通讯作者：
Chen, Qianxue
中科院分区：
文献类型：
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作者：
Lei, Junrong;Chen, Qianxue
目的：本研究旨在探讨白藜芦醇（RSV）减轻局灶性脑缺血脑损伤的分子机制。方法和材料：研究磷脂酰肌醇3激酶/Akt（PI 3 K/Akt）通路是否参与呼吸道合胞病毒（RSV）的抗炎和神经保护作用。本研究采用大脑中动脉闭塞（MCAO）动物模型。成年雄性Sprague-Dawley（SD）大鼠进行MCAO，然后在缺血发作后接受RSV或溶媒治疗。侧脑室注射PI 3 K抑制剂LY 294002以抑制PI 3 K/Akt信号通路。在MCAO后24 h评估神经功能缺损评分和脑含水量。实时荧光定量PCR检测炎症因子白细胞介素（IL）-1 β、肿瘤坏死因子（TNF α）和环氧合酶-2（COX 2）mRNA水平。MCAO后24 h测定髓过氧化物酶（MPO）活性。Western blot检测缺血脑组织磷酸化Akt和COX 2蛋白表达。结果如下：RSV可显著降低神经功能缺损评分、脑含水量和MPO酶活性，LY 294002可完全阻断RSV的上述作用。实时荧光定量PCR结果显示RSV显著抑制了炎症因子IL-1 β、TNF α、COX 2 mRNA水平的上调。RSV显著抑制MCAO后24 h COX 2蛋白表达上调，LY 294002可消除这种作用。结论：RSV主要通过PI 3 K/Akt信号通路减轻脑缺血损伤。
Objective: The aim of this study was to evaluate the potential molecular mechanism of resveratrol (RSV) that attenuates brain damage from focal cerebral ischemia. Methods and materials: To investigate whether phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway was involved in RSV anti-inflammatory and neuroprotective properties. Middle cerebral artery occlusion (MCAO) animal model was used in this study. Adult male Sprague-Dawley (SD) rats underwent MCAO, and then received treatment with RSV or vehicle after the onset of ischemia. PI3K inhibitor LY294002 was injected intracerebroventricularly to inhibit the PI3K/Akt signaling pathway. Neurological deficit scores and cerebral water content were assessed 24 h after MCAO. The inflammatory factors interleukin (IL)-1 beta, tumor necrosis factor (TNF alpha), and cyclooxygenase-2 (COX2) mRNA level were examined by real-time PCR. The enzymatic activity of myeloperoxidase (MPO) was measured 24 h after MCAO. The protein expression of phospho-Akt and COX2 in ischemic brain were determined by western blot. Results: RSV significantly reduced neurological deficit scores, cerebral water content and the enzymatic activity of MPO, all of which were abolished by LY294002 administration. Real-time PCR showed that RSV significantly suppressed the upregulation of the inflammatory factors IL-1 beta, TNF alpha, COX2 mRNA levels. RSV significantly inhibited upregulated the protein expression of COX2 24 h after MCAO, which effect was abolished by LY294002 administration. Conclusion: RSV attenuated ischemic brain damage induced by cerebral artery occlusion mainly through PI3K/Akt signaling pathway.