Irisin Peptide Protects Brain Against Ischemic Injury Through Reducing Apoptosis and Enhancing BDNF in a Rodent Model of Stroke
Irisin Peptide Protects Brain Against Ischemic Injury Through Reducing Apoptosis and Enhancing BDNF in a Rodent Model of Stroke
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DOI：
10.1007/s11064-018-2569-9
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发表时间：
2018-08-01
影响因子：
4.4
通讯作者：
Vakili, Abedin
中科院分区：
文献类型：
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作者：
Asadi, Yasin;Gorjipour, Fazel;Vakili, Abedin
有证据表明鸢尾素在脑卒中中的治疗潜力。本研究旨在评估重组鸢尾素对脑卒中小鼠模型的梗死面积、神经功能结局、血脑屏障（BBB）通透性、细胞凋亡和脑源性神经营养因子（BDNF）表达的影响。采用小鼠大脑中动脉闭塞（MCAO）45 min，再灌注23 h的方法建立小鼠短暂性局灶性脑缺血模型。在MCAO开始时，以0.1、0.5、2.5、7.5和15 μ g/kg的剂量脑室内（ICV）给予重组鸢尾素。于缺血后24 h分别采用改良神经功能评分（mNSS）、氯化三苯基四氮唑（TTC）染色和伊文思蓝（EB）外渗法评价神经功能、脑梗死面积、脑水肿和血脑屏障通透性。TUNEL法和免疫组化法检测脑组织中凋亡细胞和BDNF蛋白的表达。免疫印迹法检测Bcl-2、Bax和caspase-3蛋白的表达。以0.5、2.5、7.5和15 μ g/kg的剂量ICV施用鸢尾素显著减少了梗塞面积，而仅以7.5和15 μ g/kg的剂量改善了神经学结果（P < 0.001）。鸢尾素（7.5 μ g/kg）治疗可减轻脑水肿（P < 0.001），而不改变血脑屏障通透性（P > 0.05）。此外，鸢尾素（7.5 μ g/kg）显著减少缺血脑皮质中的凋亡细胞和增加BDNF免疫反应性（P < 0.004）。Irisin显著下调Bax和caspase-3的表达，上调Bcl-2蛋白。本研究表明，鸢尾素通过减少脑细胞凋亡和增加脑皮质BDNF蛋白表达减轻脑损伤。
Evidence has shown therapeutic potential of irisin in cerebral stroke. The present study aimed to assess the effects of recombinant irisin on the infarct size, neurological outcomes, blood-brain barrier (BBB) permeability, apoptosis and brain-derived neurotrophic factor (BDNF) expression in a mouse model of stroke. Transient focal cerebral ischemia was established by middle cerebral artery occlusion (MCAO) for 45 min and followed reperfusion for 23 h in mice. Recombinant irisin was administrated at doses of 0.1, 0.5, 2.5, 7.5, and 15 A mu g/kg, intracerebroventricularly (ICV), on the MCAO beginning. Neurological outcomes, infarct size, brain edema and BBB permeability were evaluated by modified neurological severity score (mNSS), 2,3,5-triphenyltetrazolium chloride (TTC) staining and Evans blue (EB) extravasation methods, respectively, at 24 h after ischemia. Apoptotic cells and BDNF protein were detected by TUNEL assay and immunohistochemistry techniques. The levels of Bcl-2, Bax and caspase-3 proteins were measured by immunoblotting technique. ICV irisin administration at doses of 0.5, 2.5, 7.5 and 15 A mu g/kg, significantly reduced infarct size, whereas only in 7.5 and 15 A mu g/kg improved neurological outcome (P < 0.001). Treatment with irisin (7.5 A mu g/kg) reduced brain edema (P < 0.001) without changing BBB permeability (P > 0.05). Additionally, irisin (7.5 A mu g/kg) significantly diminished apoptotic cells and increased BDNF immunoreactivity in the ischemic brain cortex (P < 0.004). Irisin administration significantly downregulated the Bax and caspase-3 expression and upregulated the Bcl-2 protein. The present study indicated that irisin attenuates brain damage via reducing apoptosis and increasing BDNF protein of brain cortex in the experimental model of stroke in mice.