基于NVU和miRNA基因网络研究三七总皂苷对脑缺血保护作用的分子机制

项目名称： 基于NVU和miRNA基因网络研究三七总皂苷对脑缺血保护作用的分子机制

项目编号： No.81460614

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 蒙兰青

作者单位： 右江民族医学院

项目金额： 47万元

中文摘要： 缺血性脑损伤发生时，神经血管单元（NVU）中的神经元、胶质细胞及微血管同时受到损伤，NVU为多方位研究缺血性脑损伤提供新靶点。miRNA参与缺血性脑损伤后NVU变化的基因网络调控，通过对药物干预后相关的miRNA进行研究，可为发现药物作用的分子机制提供新思路。三七总皂苷（PNS）临床上广泛用于脑梗死的治疗。研究发现PNS对脑缺血后的NVU具有保护作用，但是通过哪些信号通路、哪些分子靶点作用于NVU，目前不清楚。为此，本研究项目将给脑缺血损伤模型大鼠PNS干预，研究脑缺血后和PNS干预后大鼠脑组织miRNA表达谱的差异，筛选出用药后差异表达的miRNA；预测差异表达miRNA的靶基因和靶基因参与的信号通路；验证差异表达的miRNA，深入分析相关差异表达miRNA及其靶基因和信号通路与用药后NVU变化的关系；从miRNA基因调控网络层面阐明PNS在缺血性脑损伤中多作用靶点的分子机制。

中文关键词： 三七总皂苷；神经血管单元；微小核糖核酸；脑缺血

英文摘要： With the occurrence of ischemic brain damage, each component of the neurovascular unit (NVU) such as neurons, glial cells and microvascular were damaged at the same time,and it provided a new target for comprehensive study of ischemic brain injury.It was already know that miRNA involved in the gene network regulation of NVU changes after ischemic brain damage.Through the study of pharmacological intervention of specific miRNA can help to find new target point and new mechanism of drugs. Panax Notoginseng Saponins(PNS) was widely used in the clinical treatment of cerebral infarction. Studies have found that PNS has multiple targets in the protection of ischemic brain injury.PNS can be applied to multiple components of the NVU after cerebral ischemia, but the exact molecular mechanism is still unclear. This research will apply PNS in cerebral ischemia injury rat model, to study the difference of miRNA expression between brain tissue of rats after cerebral ischemic injury and after PNS intervention, to screen differentially expressed miRNA after drug,to forecast the target gene of the differentially expressed miRNA and the signal pathway of target gene involved in, to verify the differentially expressed miRNA, to analysis the relationship between the changes of neurovascular unit and the differentially expressed miRNA with it target gene and the signal pathway after the treatment, to show the molecular mechanism of that PNS has a multitargets in ischemic brain injury through the miRNA gene regulation network.

英文关键词： Panax Notoginseng Saponins;neurovascular unit;miRNA;cerebral ischemia