基于IGF1通路探讨胡萝卜苷促进缺血性脑卒中后神经功能恢复的作用及机制
结题报告
批准号:
81860221
项目类别:
地区科学基金项目
资助金额:
37.0 万元
负责人:
江励华
依托单位:
学科分类:
脑血管结构、功能异常及相关疾病
结题年份:
2023
批准年份:
2018
项目状态:
已结题
项目参与者:
江励华
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中文摘要
缺血性脑卒中(CIS)严重危害人类健康,亟待开发安全有效的药物。胰岛素样生长因子(IGF1)能保护神经血管单元(NVU,包括神经元、血管内皮细胞、星形胶质细胞等),促进其重塑,促进神经功能恢复。我们已发现胡萝卜苷能促进多种细胞表达IGF1,活化IGF1通路。本课题研究其对CIS的治疗作用,分为整体动物实验和细胞实验,观察其生物效应并探讨作用机制。整体实验:胡萝卜苷经鼻腔给药,作用于改良的CIS模型(SD大鼠饲喂高脂饲料+大脑中动脉栓塞再灌注),运用免疫荧光、激光共聚焦扫描、免疫印迹、膜片钳和同步辐射相位衬度显微断层成像等方法和技术,观察其对NVU保护、重塑及对神经功能恢复的作用。细胞实验:研究胡萝卜苷对体外NVU半暗带损伤模型的保护作用。机制研究:检测胡萝卜苷是否激活IGF1通路,其作用是否被IGF1R抑制剂所抑制。本研究为CIS治疗提供新的药物和思路。
英文摘要
Cerebral ischemic stroke (CIS) causes serious damage to human health and life. Thus, the need to find efficient neuroprotectant drugs with minimal side effectsis is becoming an urgency. IGF1 can restore nervous system by protecting neurovascular unit (NVU) and promoting NVU remodelling for the importance of NVU, which consists of neurons, endothelial cells, astrocytes and so on. We previously reported that daucosterol promoted the expression of IGF1 in multiple cells,activating the IGF1 signal pathway. In the present study, we research the therapeutical effects of daucosterol on CIS. High fat diet rats subjected to cerebral ischemia/reperfusion injury are treated with nasal administration of daucosterol. The effects of daucosterol on the protection and remodelling of NVU, such as vascular proliferation, astrocytes activation, neuronal regeneration, neural plasticity, and the recovery of neurological function are measured by some research methods and techniques,such as immunofluorescence, confocal laser scanning, western-blot, patch clamp, and synchrotron radiation (SR) X-ray in line phase contrast imaging, and so on. In the cell experiments, we study the effects of protection on penumbra injured NVU model. Also, we detect if IGF1 signal pathway is activated by daucosterol, and use the inhibitor of IGF1R to study the mechanism of the effects. The present study provides a new medicine for CIS treatment, and a new strategy for developing new drugs to treat CIS.
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