Hyperforin promotes post-stroke functional recovery through interleukin (IL)−17A-mediated angiogenesis
Hyperforin promotes post-stroke functional recovery through interleukin (IL)−17A-mediated angiogenesis
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DOI：
10.1016/j.brainres.2016.06.025
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发表时间：
2016-09
期刊：
影响因子：
2.9
通讯作者：
Jiancheng Zhang;Cheng-ye Yao;Jiayi Chen;Yujing Zhang;Shi-ying Yuan;Yun Lin
中科院分区：
文献类型：
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作者：
Jiancheng Zhang;Cheng-ye Yao;Jiayi Chen;Yujing Zhang;Shi-ying Yuan;Yun Lin
贯叶金丝桃素是药用植物贯叶金丝桃的主要活性成分，已被证明对急性缺血性中风具有神经保护作用。然而，贯叶金丝桃素对脑卒中后功能恢复的长期作用及其机制尚未见报道。C57 BL/6野生型小鼠或白细胞介素（IL）-17A基因敲除小鼠经历大脑中动脉闭塞（60分钟），然后再灌注28天。在这里，我们发现，延迟治疗与贯叶金丝桃素显着促进功能恢复和增加IL-17 A的表达在缺血后28天（dpi）的缺血半球。IL-17 A敲除或抗IL-17 A单克隆抗体（mAb）处理显著减弱贯叶金丝桃素对功能恢复的促进作用。筛选神经营养因子后，我们发现阻断IL-17 A显著降低，而重组小鼠IL-17 A（rIL-17 A）治疗显著增加血管内皮生长因子（VEGF）的表达。我们的数据还显示，rIL-17 A治疗显著增加CD 34表达，并促进28 dpi时的功能恢复，而VEGF中和抗体治疗则减弱了这种促进作用。此外，贯叶金丝桃素治疗显著增加VEGF和CD 34在缺血半球在28 dpi的表达，并通过阻断IL-17 A的影响减弱。VEGF中和抗体可明显减弱贯叶金丝桃素对脑组织CD 34表达的促进作用。因此，我们的研究结果表明，除了急性神经保护时，立即交付缺血性中风后，贯叶金丝桃素也可以促进功能恢复时，交付中风恢复的后期阶段。我们的研究结果还揭示了一个以前未表征的属性IL-17 A/VEGF信号诱导的血管生成贯叶金丝桃素介导的功能恢复。
Hyperforin, the main active ingredient of the medicinal plant Hypericum perforatum, has been shown to be neuroprotective against acute ischemic stroke. However, the long-term actions of hyperforin on the post-stroke functional recovery and underlying mechanisms have not been investigated. C57BL/6 wild-type mice or interleukin (IL)−17A knock-out mice underwent middle cerebral artery occlusion (60 min) followed by reperfusion for 28 days. Here, we found that delayed treatment with hyperforin significantly promoted functional recovery and increased IL-17A expression in the ischemic hemisphere at 28 days post-ischemia (dpi). IL-17A knock-out or anti-IL-17A monoclonal antibody (mAb) treatment significantly attenuated the promoting effects of hyperforin on functional recovery. After screening for neurotrophic factors, we revealed that blocking IL-17A significantly decreased, whereas recombinant mouse IL-17A (rIL-17A) treatment significantly increased vascular endothelial growth factor (VEGF) expression. Our data also showed that rIL-17A treatment significantly increased CD34 expression and promoted functional recovery at 28 dpi, and the promoting effects were attenuated by VEGF neutralizing antibody treatment. Furthermore, hyperforin treatment significantly increased the expression of VEGF and CD34 in the ischemic hemisphere at 28 dpi, and the effects were attenuated by blocking IL-17A. Furthermore, VEGF neutralizing antibody significantly attenuated the promoting role of hyperforin on the cerebral CD34 expression. Thus, our results suggest that, in addition to the acute neuroprotection when delivered immediately after ischemic stroke, hyperforin could also promote functional recovery when delivered in the later phases of stroke recovery. Our results also reveal a previously uncharacterized property of IL-17A/VEGF signaling-induced angiogenesis in hyperforin-mediated functional recovery.