Cystatin C对脑缺血后海马神经发生的影响及机制

项目名称： Cystatin C对脑缺血后海马神经发生的影响及机制

项目编号： No.81460186

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： 梁雪云

作者单位： 宁夏医科大学

项目金额： 47万元

中文摘要： 血管性痴呆发病率逐年升高，临床仍无有效治疗方法。脑缺血后，海马区Cystatin C（Cys C）表达水平增高，Cys C已被发现参与神经发生过程，但其功能仍不清楚。前期研究中发现，脑缺血患者血清中存在Cys C寡聚体，Cys C寡聚体对脑缺血后海马神经发生的功能及机制研究较少。本项目拟利用小鼠慢性脑缺血模型，采用组织学及分子生物学技术观察脑缺血后Cys C在海马区表达特点，并结合脑缺血后海马区神经发生的变化，探讨脑缺血后CysC对海马区神经发生的影响；利用体外海马神经干细胞培养体系，观察不同条件下，不同结构形式的Cys C对海马神经干细胞的增殖能力，迁移及分化过程的影响；通过在培养体系中添加MAPK通路抑制剂，观察Cys C对神经发生影响的变化，探讨Cys C通过MAPK通路影响神经发生的机制。探明脑缺血后Cys C对神经发生的影响和机制，将为临床寻找治疗血管性痴呆提供一种新的思路。

中文关键词： Cystatin；C；神经发生；脑缺血；海马

英文摘要： With the increased incidence of ischemia, more and more people are suffered from vascular dementia (VD). There is still no effective method for clinical therapy on VD, as its unclear mechanism. Previous studies have proved that the neurogenesis in hippocampus has played a role in the formation process of cognitions. Usually, the neurogenesis in hippocampus becomes active after ischemia, some study showed that most of the neural stem cell differentiated into glial cell after ischemia, which may damage the neuron. The change of neurogenesis after ischemia may affect on the patient's cognitions. The main regulation factors about neurogenesis and their related mechanisms still needed to be studied. It would be benefit to the clinical therapy on VD when the main regulation factors about neurogenesis and their related mechanisms are clarified. Cystatin C(Cys C) is targeted many pathological physiology process of neurological disease, but its definite function is still unclear. Previous study showed the expression level of Cys C was significant increase in hippocampal region after ischemia. Cys C is inclined to formation oligomer, which might lead to different effects of Cys C on neural cell. We have proved that Cys C played a role in neuronal apoptosis and induced the tyrosine hydroxylase gene expression in differentiated neuronal cell through JNK pathway. The oligomer of Cys C has been detected in the serum of the ischemic patient in our study. We hypothesized that the effect of Cys C on the process of hippocampal neurogenesis after ischemia may be different between Cys C monomer and Cys C oligomer. In this study, we want to study the change of the neurogenesis process in the hippocampus after ischemia and the involvement of Cys C monomer and Cys C oligomer in the neurogenesis process by an established ischemic mouse model and cell culture system. We will evaluate the neurogenesis change through examining the proliferation , migration and differentiation of the neural stem cell using Brd U staining, immuno-histochemical staining, laser capture microdessection, Real Time PCR and Western blotting.We aim to provide an useful basic theory for the clinical therapy on VD.

英文关键词： Cystatin C;Neurogenesis;Ischemia;Hippocampus