Irisin Contributes to Neuroprotection by Promoting Mitochondrial Biogenesis After Experimental Subarachnoid Hemorrhage.
Irisin Contributes to Neuroprotection by Promoting Mitochondrial Biogenesis After Experimental Subarachnoid Hemorrhage.
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鸢尾素通过促进实验性蛛网膜下腔出血后的线粒体生物发生来促进神经保护
DOI：
10.3389/fnagi.2021.640215
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发表时间：
2021
影响因子：
4.8
通讯作者：
Jiang Y
中科院分区：
文献类型：
--
作者：
Tu T;Yin S;Pang J;Zhang X;Zhang L;Zhang Y;Xie Y;Guo K;Chen L;Peng J;Jiang Y
蛛网膜下腔出血（Subarachnoid hemorrhage，SAH）是一种严重的脑卒中，给临床带来了一系列棘手的挑战。线粒体内稳态失衡被认为是SAH后早期脑损伤（EBI）级联反应的重要病理机制。Irisin是一种与代谢和线粒体稳态相关的蛋白质，已被报道在卒中后神经保护中发挥关键作用。然而，这种肌因子是否能在SAH后发挥神经保护作用仍不清楚。在本研究中，我们探讨了鸢尾素的保护作用和相关的线粒体生物合成在SAH动物模型的潜在机制。采用血管内穿孔诱导SAH，侧脑室注射重组鸢尾素。进行神经行为评估、TdT-UTP缺口末端标记（TUNEL）染色、二氢乙锭（DHE）染色、免疫荧光、蛋白质印迹和透射电子显微镜（TEM）用于SAH后评估。我们证明，鸢尾素治疗改善神经行为评分，减少神经元凋亡，并减轻氧化应激EBI后SAH。更重要的是，外源性鸢尾素的管理，保护线粒体的形态和促进线粒体的生物合成。线粒体解偶联蛋白-2（UCP-2）抑制剂可部分逆转鸢尾素的保护作用。综上所述，鸢尾素可能通过改善线粒体生物合成，至少部分通过UCP-2相关靶点，对SAH具有神经保护作用。
Subarachnoid hemorrhage (SAH) is a devastating form of stroke, which poses a series of intractable challenges to clinical practice. Imbalance of mitochondrial homeostasis has been thought to be the crucial pathomechanism in early brain injury (EBI) cascade after SAH. Irisin, a protein related to metabolism and mitochondrial homeostasis, has been reported to play pivotal roles in post-stroke neuroprotection. However, whether this myokine can exert neuroprotection effects after SAH remains unknown. In the present study, we explored the protective effects of irisin and the underlying mechanisms related to mitochondrial biogenesis in a SAH animal model. Endovascular perforation was used to induce SAH, and recombinant irisin was administered intracerebroventricularly. Neurobehavioral assessments, TdT-UTP nick end labeling (TUNEL) staining, dihydroethidium (DHE) staining, immunofluorescence, western blot, and transmission electron microscopy (TEM) were performed for post-SAH assessments. We demonstrated that irisin treatment improved neurobehavioral scores, reduced neuronal apoptosis, and alleviated oxidative stress in EBI after SAH. More importantly, the administration of exogenous irisin conserved the mitochondrial morphology and promoted mitochondrial biogenesis. The protective effects of irisin were partially reversed by the mitochondrial uncoupling protein-2 (UCP-2) inhibitor. Taken together, irisin may have neuroprotective effects against SAH via improving the mitochondrial biogenesis, at least in part, through UCP-2 related targets.
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