星形胶质细胞源性IL-17A调控丰富环境下脑缺血损伤后血管新生的作用机制

血管新生与脑缺血损伤后神经功能重塑密切相关。最近研究发现星形胶质细胞来源的IL-17A在脑缺血损伤后慢性期有促血管新生作用，其机制可能与调控VEGF的转录与活化有关。我们前期研究证实丰富环境可以促进星形胶质细胞增生和血管新生，但两者的关系仍需进一步研究。我们假设，在脑缺血损伤慢性期，丰富环境促进星形胶质细胞源性IL-17A的表达与释放，后者通过IL-6/Stat3信号通路影响VEGF的表达并促进血管新生，进而改善神经功能。本课题拟通过以下研究阐明IL-17A通路在丰富环境调控下脑缺血损伤后血管新生中的作用机制：1）丰富环境对脑缺血损伤大鼠的促血管新生作用是否与IL-17A表达有关；2）体外细胞验证IL-17A促血管新生作用是否通过上调IL-6/Stat3进而促进 VEGF的表达来实现的。为脑缺血损伤慢性期 IL-17A介导的神经修复机制研究开拓新的思路。

Angiogenesis is closely related to neurological remodeling after cerebral ischemic injury. Recently, it has been found that astrocyte-derived IL-17A promoted angiogenesis in the chronic phase of cerebral ischemic injury through the regulation of VEGF transcription and activation. Our previous studies have demonstrated that enriched environment (EE) could promote astrocyte proliferation and angiogenesis, but the relationship between them needs further study. We proposed that EE could promote the secretion of IL-17A from astrocytes in the later phase of cerebral ischemic injury. Astrocytic IL-17A could upregulate the IL-6 / STAT3 pathway which could regulate the transcription and activation of VEGF and eventually enhance angiogenesis and improve the neurological function. The purpose of this study is to clarify the mechanism of enriched environment on astrocytic IL-17A mediated angiogenesis after cerebral ischemic injury: 1) whether the effect of enriched environment on angiogenesis in rats after cerebral ischemic injury is related to the expression of IL-17A; 2) whether the effect of IL-17A on angiogenesis is achieved by up-regulating IL-6/Stat3 and thus promoting the VEGF expression in vitro. It opens up new ideas for the study of IL-17A-mediated neural repair mechanism in the chronic stage of cerebral ischemia injury.