【摘要】 目的:阐明卒中后抑郁与炎症之间的关系,以及该过程中N-甲基-D-天冬氨酸受体(NMDAR)对于NLRP3-caspase-1通路的影响。方法:以大脑中动脉栓塞(MCAO)模型联合大鼠悬尾实验(TST)模型构建大鼠卒中后抑郁模型,按实验要求分为Control组、MCAO组,PSD组(MCAO+TST组)、PSD+D-丝氨酸干预组(MCAO+TST+D组)、PSD+氯胺酮干预组(MCAO+TST+K组)共5组。以糖水消耗实验及血清5-HT检测评估大鼠精神状态,通过ELISA、Western Blot、real-time PCR等方法检测NLRP3-caspase-1通路相关分子的变化。随后采用D-丝氨酸及氯胺酮等对NMDAR的活性进行调节,以糖水消耗实验及血清5-HT,ELISA、Western Blot、Real-time PCR等方法进一步观察对上述指标的影响。结果:与Control组相比,MCAO组中的大鼠,其血清5-HT的水平以及糖水消耗比变化不明显(P> 0. 5),但NLRP3-caspase-1通路出现了激活(P <0. 001); MCAO+TST组中,大鼠血清的5-HT及糖水消耗比明显下降,NLRP3-caspase-1通路相关分子出现了明显活化(P <0. 001);而通过应用NMDA受体共激动剂D-丝氨酸干预,在MCAO+TST+D组中,大鼠糖水消耗比及血清5-HT出现了进一步的下降,同时NLRP3-caspase-1通路相关分子的激活较前更为明显(P <0. 001);而应用NMDA受体拮抗剂氯胺酮后,MCAO+TST+K组中,大鼠糖水消耗比及血清5-HT较前明显提高,同时NLRP3-caspase-1通路相关分子的激活较前出现了下调(P <0. 001)。结论:NLRP3-caspase-1通路所代表的炎症反应过程与卒中后抑郁的发生发展密切相关,而通过干预与其密切相关的NMDA受体,可实现对该过程的调控,起到影响卒中后抑郁程度的作用。更多还原

【Abstract】 Objective: To elucidate the relationship between post-stroke depression and inflammation,and the effect of NMDA receptor on NLRP3-caspase-1 pathway in this process. Methods: A rat model of post-stroke depression was established by using the middle cerebral artery occlusion( MCAO) model combined with the tail suspension test( TST) model.According to the experimental requirements,aninrals were divided into 5 groups as follows: Control group,MCAO group,post-stroke depression( PSD) group( MCAO + TST group),PSD and D-serine intervention group( MCAO + TST + D group),PSD and ketamine intervention group( MCAO + TST + K group). The mental state of rats was evaluated by saccharide consumption test and serum 5-HT assay. The changes of NLRP3-caspase-1 pathway-related molecules were detected by ELISA,Western Blot and real-time PCR. Subsequently,the activity of NMDA receptors was perturbed with D-serine and ketamine to observe changes in the mental state of rats assessed by using saccharide consumption test andserum 5-HT assay,and changes in molecules related to NLRP3-caspase-1 pathway by using ELISA,Western Blot and Real-time PCR. Results: Compared with the control group,there was no obvious change in the 5-HT and sugar consumption ratios in the MCAO group( P > 0. 05),but the NLRP3-caspase-1 pathway was activated( P < 0. 001). In the MCAO +TST group,the serum 5-HT and sugar consumption ratios of the mouse decreased significantly,and the NLRP3-caspase-1 pathway-related molecules showed significant activation( P < 0. 001). By using the NMDA receptor co-agonist D-serine in the MCAO + TST + D group,the sugar consumption ratio and serum 5-HT showed further decrease than before,and the activation of NLRP3-caspase-1 pathway-related molecules was more obvious than before( P < 0. 001). By using the NMDA receptor antagonist ketamine in the MCAO + TST + K group,the sugar consumption ratio and serum 5-HT of the rats were significantly higher than before,and the activation of NLRP3-caspase-1 pathway-related molecules was down-regulated( P < 0. 001). Conclusion: The inflammatory process represented by the NLRP3-caspase-1 pathway is closely related to the development of post-stroke depression. Intervening the NMDA receptors which is closely related with NLRP3-caspase-1 pathway,can regulate the inflammatory process and further intervene the development of post-stroke depression.更多还原