白介素18在脑卒中后抑郁炎症机制中的作用研究

项目名称： 白介素18在脑卒中后抑郁炎症机制中的作用研究

项目编号： No.81200893

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 杨玲俐

作者单位： 苏州大学

项目金额： 24万元

中文摘要： 细胞因子假说是近年提出的与卒中后抑郁（PSD）相关的新假说，它认为脑缺血所致情感调节相关脑区致炎性细胞因子产生增加可能与PSD的发生相关。我们的前期临床研究发现：缺血性卒中发病24h内入院的PSD患者入院第七天血清白介素18（IL-18）水平显著高于非抑郁卒中患者，提示IL-18可能参与PSD的炎症机制。本项目将通过建立实验性PSD小鼠模型，分别观测IL-18和吲哚胺2,3双加氧酶（IDO）在PSD状态下在小鼠脑组织的表达并测定IDO酶活性，探讨其与抑郁行为发生的关系，应用IL-18敲除小鼠，判别IL-18正常和缺如表达情况下IDO表达和酶活性变化及PSD发生情况，并进一步探讨SSRI抗抑郁剂、抗炎性细胞因子IL-1RA及IL-18抑制剂的干预效果及分子机制。本研究期望阐明IL-18在PSD炎症机制中的作用，为PSD有效治疗提供新的实验依据，也将为探讨PSD分子机制提供新的思路和证据。

中文关键词： 卒中；卒中后抑郁；行为学检测；吲哚胺2;3双加氧酶；白介素18

英文摘要： Poststroke depression (PSD) is a common complication of stroke. Current research interests mainly focus on the pathogenesis, prevention and treatment of PSD. Recenlty the cytokine hypotheses proposed that, cerebral ischemia-induced production of proinflammatary cytokines in emotional regulation related brain areas might be related to the incidence of PSD. In our prelimiary clinical study, we followed up one hundred ischemic stroke patients admitted to the hospitals within the first 24 hours after stroke onse. Our results showed that serum IL-18 on day 7 post admission was significantly higher in poststroke depression patients than that in non-post-stroke depression patients. Therefore, we hypotheisize that IL-18 is involved in the inflammatory mechanisms of PSD. In this proposal, we will establish an experiment PSD mouse model, measure the production of IL-18, and the expression and activity of IDO in brain tissues, and determine if IL-18 and IDO is related to depressive behaviors. Further, we will investigate if the absence of IL-18 will affect the expression and activity of IDO and the occurrence of PSD in IL-18 knock-out mice. Furthermore, we will investigate the effect and molecular mechanisms of PSD treatment with SSRI antidepressant, anti-inflammatory cytokine IL-1RA and IL-18 inhibitor.The aim of this pro

英文关键词： stroke；post-stroke depression；behavioral tests；IDO；IL-18