bFGF plays a neuroprotective role by suppressing excessive autophagy and apoptosis after transient global cerebral ischemia in rats.
bFGF plays a neuroprotective role by suppressing excessive autophagy and apoptosis after transient global cerebral ischemia in rats.
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bFGF 通过抑制大鼠短暂性全脑缺血后的过度自噬和细胞凋亡发挥神经保护作用
DOI：
10.1038/s41419-017-0229-7
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发表时间：
2018-02-07
影响因子：
9
通讯作者：
Cui D
中科院分区：
文献类型：
--
作者：
Sun D;Wang W;Wang X;Wang Y;Xu X;Ping F;Du Y;Jiang W;Cui D
短暂性全脑缺血（tGCI）是一种脑血管疾病，可导致神经元凋亡损伤和功能缺陷。碱性成纤维细胞生长因子（bFGF）在中枢神经系统（CNS）高度表达，对多种CNS疾病具有神经保护作用。然而，bFGF对tGCI的影响尚未深入研究。本研究旨在探讨bFGF在tGCI动物模型中的作用及其机制。脑室内（i.c.v.）注射bFGF后，观察到功能改善，并且在缺血脆弱的海马CA1区存活神经元的数量增加。tGCI后诱导细胞凋亡，bFGF治疗可通过抑制p53线粒体易位来减弱细胞凋亡。此外，自噬在此过程中被激活，bFGF可以通过mTOR通路抑制自噬的激活。利用自噬激活剂雷帕霉素探讨bFGF、细胞凋亡和自噬之间的关系。雷帕霉素处理后，细胞凋亡恶化，这表明过度的自噬可能有助于细胞凋亡过程。总之，这些结果表明，bFGF可以发挥神经保护作用，在海马CA1区通过抑制过度自噬mTOR途径和抑制凋亡，防止p53线粒体易位。此外，我们的研究结果表明，bFGF可能是一种有前途的治疗剂，用于治疗tGCI的主要不良事件，包括心脏骤停，休克，体外循环，创伤性出血和窒息。
Transient global cerebral ischemia (tGCI) is a cerebrovascular disorder that can cause apoptotic neuronal damage and functional deficits. Basic fibroblast growth factor (bFGF) was reported to be highly expressed in the central nervous system (CNS) and to exert neuroprotective effects against different CNS diseases. However, the effects of bFGF on tGCI have not been studied intensively. This study was conducted to investigate the effect of bFGF and its underlying mechanism in an animal model of tGCI. After intracerebroventricular (i.c.v.) injection of bFGF, functional improvement was observed, and the number of viable neurons increased in the ischemia-vulnerable hippocampal CA1 region. Apoptosis was induced after tGCI and could be attenuated by bFGF treatment via inhibition of p53 mitochondrial translocation. In addition, autophagy was activated during this process, and bFGF could inhibit activation of autophagy through the mTOR pathway. Rapamycin, an activator of autophagy, was utilized to explore the relationship among bFGF, apoptosis, and autophagy. Apoptosis deteriorated after rapamycin treatment, which indicated that excessive autophagy could contribute to the apoptosis process. In conclusion, these results demonstrate that bFGF could exert neuroprotective effects in the hippocampal CA1 region by suppressing excessive autophagy via the mTOR pathway and inhibiting apoptosis by preventing p53 mitochondrial translocation. Furthermore, our results suggest that bFGF may be a promising therapeutic agent to for treating tGCI in response to major adverse events, including cardiac arrest, shock, extracorporeal circulation, traumatic hemorrhage, and asphyxiation.
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