RKIP对脑卒中的保护作用及其影响机制

项目名称： RKIP对脑卒中的保护作用及其影响机制

项目编号： No.81202532

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 药物学、药理学

项目作者： 张秀花

作者单位： 中国人民解放军第二军医大学

项目金额： 23万元

中文摘要： 脑卒中一旦发生后果严重，防止其发生非常重要。SHR-SP是从SHR定向培育的具自发性脑卒中倾向的亚种，到一定年龄就发生脑卒中并死亡。我们发现，大脑中动脉栓塞后SHR-SP脑梗死面积显著大于SHR，说明同样缺血状态下SHR-SP比SHR更敏感。为进一步探讨这种差异的机制，我们以蛋白质组学研究SHR-SP脑蛋白质表达变化，结果发现：与SHR相比，RKIP在SHR-SP脑中表达显著减少，进而我们以Realtime-PCR验证了该结果。据此，我们推测RKIP表达减少在SHR-SP脑卒中发生过程中很可能起重要作用。为验证该假设，本课题拟分别从离体细胞和整体动物水平进行以下研究：确定SHR-SP易发生脑卒中与RKIP表达减少有关；进一步探讨RKIP表达减少导致SHR-SP易发脑卒中的机制。本研究可为预防脑卒中发生提供有效作用靶点，为减少脑卒中发生探索一个行之有效的治疗方法，为脑卒中的治疗提供新的思路。

中文关键词： Raf激酶抑制蛋白；脑卒中；MAPK通路；NF-κB通路；糖氧剥夺模型

英文摘要： Stroke remains to be the primary cause of adult disability and ranks only behind cancer and cardiac disease as a cause of death worldwide. Interestingly, a similar variation in susceptibility to stroke occurs in spontaneously hypertensive rats (SHR), and thus a sub-strain of SHR was developed based on their susceptibility to stroke and named stroke-prone spontaneously hypertensive rats (SHR-SP),which develop a stroke at a mean age of 10 (males) to 14 months (females). We speculated that since both strains (SHR and SHR-SP) were hypertensive, a comparison of SHR-SP with SHR would provide new insights into the pathogenesis and development of stroke beyond hypertension. Our results showed that the area of cerebral infarction after middle cerebral artery occlusion (MCAO) of SHR-SP was significantly larger than that of SHR, suggesting that SHR-SP is more susceptible to ischemic stroke than SHR. To further reveal the mechanisms of this difference, we examined the differentially expressed protein profiles in the brains of SHR-SP and SHR by using two dimensional fluorescent difference gel electrophoresis (2D-DIGE). We firstly found that Raf kinase inhibitor protein (RKIP) was significantly down-regulated in SHR-SP, and this result has been confirmed by Realtime-PCR. Based on these findings; we speculated that the decre

英文关键词： RKIP；cerebral apoplexy；MAPK pathway；NF-κB pathway；OGD