NLRP3炎性小体表达下调对卒中后抑郁大鼠的作用  

Effect of down-regulation of NLRP3 inflammasome on post-stroke depression in rats

作　　者：刘柳[1] 蒋超[1] 李芳芳[1] LIU Liu;JIANG Chao;LI Fangfang(Department of Neurology,the Fifth Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第五附属医院神经内科

出　　处：《中国实用神经疾病杂志》2019年第8期813-820,共8页Chinese Journal of Practical Nervous Diseases

基　　金：国家自然科学基金资助项目面上项目(编号:81671165)

摘　　要：目的研究NLRP3炎性小体对卒中后抑郁大鼠抑郁行为及神经功能的影响,以期发现卒中后抑郁的可能治疗靶点。方法 144只SD大鼠进行大脑中动脉闭塞术建立缺血再灌注模型(middle cerebral artery occlusion,MCAO),然后随机分为4组:假手术组(n=12)、PSD(post-stroke depression,卒中后抑郁)组(n=12)、PSD+control siRNA组(n=12)、PSD+NLRP3 siRNA组(n=12)。PSD组大鼠进行左侧大脑中动脉闭塞术后,再进行慢性轻度不可预见性应激(chronic mild unpredictable stress,CUMS)联合单居21 d,假手术组操作与PSD组相同,但颈内动脉不放置线栓,也不进行慢性轻度不可预见性应激联合单居处理。CUMS第21天,将NLRP3 siRNA或等体积control siRNA、无菌生理盐水微量注射至SD大鼠侧脑室以下调NLRP3炎性小体的表达,检测PSD后第1、7、14天各组大鼠的抑郁行为评分(蔗糖水偏好试验、悬尾试验)和神经功能(足错误试验、Longa评分),并用ELISA检测脑组织中IL-1β、IL-18的含量。结果与PSD+control NLRP3组相比,PSD+NLRP3 siRNA组大鼠在PSD后第1、7、14天脑组织中IL-1β、IL-18表达降低(P<0.05),糖水偏好比例增高、悬尾时静止不动时间减少,足错误次数增加,Longa评分降低(P<0.05)。结论抑制NLRP3炎性小体可减轻PSD大鼠的抑郁行为,促进神经功能恢复。Objective To study the effect of NLRP3 inflammasome on depressive behavior and neurological recovery in post-stroke depression rats,so as to find possible therapeutic targets for post-stroke depression.Methods 144 SD rats were performed middle cerebral artery occlusion(MCAO),then randomly divided into four groups:sham-operated group(n=12/group),PSD group(n=12/group),PSD(post-stroke depression)+control siRNA group(n=12/group),PSD +NLRP3 siRNA group(n=12/group).In PSD group,rats were subjected to left middle cerebral artery occlusion,followed by chronic mild unpredictable stress(CUMS) combined with solitary living for 21 days.The sham-operated group performed the same operation as PSD group,but the internal carotid artery was not subjected to thread embolization or CUMS.On the 21 st day of CUMS,NLRP3 siRNA or the same volume of control siRNA and sterile saline were microinjected into the lateral ventricle of SD rats to down-regulate the expression of NLRP3 inflammasome.Depression behavior scores(sucrose preference test and tail suspension test) and neurological function(foot error test and Longa score) were measured on the day of 1,7 and 14 after PSD.ELISA was used to detect the contents of IL-1β and IL-18 in brains of rats.Results Compared with PSD+control NLRP3 group,the expression of IL-1β and IL-18 in the brains of PSD+NLRP3 siRNA group decreased on the day of 1,7 and 14 after PSD(P<0.05),and the proportion of sugar preference increased,the time of resting decreased,the number of foot errors increased,and the Longa score decreased(all P<0.05).Conclusion Inhibition of NLRP3 inflammasome can reduce the depression behavior of PSD rats and promote the recovery of neurological function.

关 键 词：NLRP3炎性小体 卒中后抑郁 神经功能 糖水偏好试验 Longa评分 

分 类 号：R332[医药卫生—人体生理学]