Yonkenafil: A novel phosphodiesterase type 5 inhibitor induces neuronal network potentiation by a cGMP-dependent Nogo-R axis in acute experimental stroke
Yonkenafil: A novel phosphodiesterase type 5 inhibitor induces neuronal network potentiation by a cGMP-dependent Nogo-R axis in acute experimental stroke
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Yonkenafil：一种新型 5 型磷酸二酯酶抑制剂在急性实验性中风中通过 cGMP 依赖性 Nogo-R 轴诱导神经元网络增强
DOI：
10.1016/j.expneurol.2014.07.007
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发表时间：
2014-11-01
影响因子：
5.3
通讯作者：
Yang, Jingyu
中科院分区：
文献类型：
--
作者：
Chen, Xuemei;Wang, Nannan;Yang, Jingyu
Yonkenafil是一种新型的磷酸二酯酶5（PDE 5）抑制剂。在这里，我们评估了yonkenafil对缺血性损伤的影响及其可能的作用机制。雄性Sprague-Dawley大鼠进行大脑中动脉闭塞，随后在2小时后开始用约肯那非进行腹膜内或静脉内治疗。在再灌注后第1天或第7天进行行为学测试。脑卒中后24 h行Nissl染色、Fluoro-Jade B染色和电镜观察，并分析梗死体积和水肿程度。cGMP依赖性Nogo-66受体（Nogo-R）通路组分、hsp 70、apaf-1的水平。24 h后检测caspase-3、caspase-9、突触素、PSD-95/神经元型一氧化氮合酶（nNOS）、脑源性神经营养因子（BDNF）/原肌球蛋白相关激酶B（Trk B）和神经生长因子（NGF）/原肌球蛋白相关激酶A（TrkA）。Yonkenafil显著抑制梗死和水肿，即使给药延迟至卒中发作后4小时。这种保护作用与神经功能的改善有关，并持续7天。Yonkenafil扩大了半影区的范围，减少了缺血细胞凋亡和神经元的丢失，并调节了Nogo-R通路中蛋白质的表达。此外，yonkenafil保护突触的结构和增加突触素的表达。BDNF/TrkB和NGF/frkA。总之，yonkenafil保护中风后神经元网络免受损伤。(C)2014 Elsevier Inc. All rights reserved.
Yonkenafil is a novel phosphodiesterase type 5 (PDE5) inhibitor. Here we evaluated the effect of yonkenafil on ischemic injury and its possible mechanism of action. Male Sprague-Dawley rats underwent middle cerebral artery occlusion, followed by intraperitoneal or intravenous treatment with yonkenafil starting 2 h later. Behavioral tests were carried out on day 1 or day 7 after reperfusion. Nissl staining, Fluoro-Jade B staining and electron microscopy studies were carried out 24 h post-stroke, together with an analysis of infarct volume and severity of edema. Levels of cGMP-dependent Nogo-66 receptor (Nogo-R) pathway components, hsp70, apaf-1. caspase-3, caspase-9, synaptophysin, PSD-95/neuronal nitric oxide synthases (nNOS), brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) and nerve growth factor (NGF)/tropomyosin-related kinase A (TrkA) were also measured after 24 h. Yonkenafil markedly inhibited infarction and edema, even when administration was delayed until 4 h after stroke onset. This protection was associated with an improvement in neurological function and was sustained for 7 d. Yonkenafil enlarged the range of penumbra, reduced ischemic cell apoptosis and the loss of neurons, and modulated the expression of proteins in the Nogo-R pathway. Moreover, yonkenafil protected the structure of synapses and increased the expression of synaptophysin. BDNF/TrkB and NGF/frkA. In conclusion, yonkenafil protects neuronal networks from injury after stroke. (C) 2014 Elsevier Inc. All rights reserved.