炎性疼痛致大鼠空间记忆损害和海马CA1区IL-6表达上调

摘要

目的: 研究炎性疼痛对大鼠空间记忆功能和海马CA1区白细胞介素-6(IL-6)表达的影响及帕瑞昔布钠对其的干预作用.方法:将30只健康的SD雄性大鼠随机分为假手术组(SO组)、炎性疼痛模型组(I组)及造模后腹腔注射帕瑞昔布钠组(P组),I组及P组大鼠采用右后肢踝关节外侧皮下注射弗氏完全佐剂方法制备炎性制痛模型,C组注射等量生理盐水;P组于造模前1天至造模后第5天腹腔注射帕瑞昔布钠[1 mL/(kg·d)],SO组和I组大鼠注射等量生理盐水;3组大鼠在术前和术后进行Morris水迷宫定位航行训练,记录大鼠穿越平台次数及平台象限停留时间;采用电子测痛仪和热刺痛仪记录各组大鼠术后第1、3和5天右后足机械缩足阈值(MWT)和热缩足潜伏期(TWL);断头处死大鼠,采用Western Blot法测定大鼠海马CA1区IL-6表达水平.结果:与SO组相比,I组大鼠术后各时间点MWT和TWL明显下降(P<0.05),穿越平台次数及平台所在象限停留时间明显减少(P<0.05),海马CA1区IL-6表达明显升高(P<0.05);与I组相比,P组术后各时间点MWT和TWL升高(P<0.05),穿越平台次数及平台所在象限停留时间明显增加(P<0.05),海马CA1区IL-6表达明显降低(P<0.05).结论:炎性疼痛可导致大鼠痛阈及空间记忆功能下降,帕瑞昔布钠可减轻上述改变,其机制可能与抑制海马CA1区IL-6表达有关.%Objective: To explore the effect of inflammatory pain on rat spatial memory function as well as interleukin-6 (IL-6) expression level in hippocampus CA1 and the intervention effect of parecoxib sodium on them.Methods:30 healthy male Sprague-Dawley rats were divided into 3 groups (n=10 in each group) randomly: sham operated group (SO group), inflammatory pain group (I group), the intraperitoneal injection of parecoxib sodium after modeling group (P group).The model of inflammatory pain was prepared by subcutaneous CFA to the lateral right hind ankle, and I Group and P group were injected with normal saline instead.P group was intraperitoneally injected with parecoxib Cdium (1 mL/kg) from the first day to the fifth day after molding, and the other two groups were given normal saline instead.3 groups of rats underwent the training of Morris water maze positioning before and after operation, and the number of rats traversing platform and the residence time of platform quadrant were recorded.Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of right hind legs were measured on 1st, 3rd, and 5th day after operation respectively by the electronic pain threshold detector and sting thermal imager.After Morris water maze experiment, rats were decapitated to measure the expression of IL-6 protein in hippocampus CA1 by Western Blot methods.Results:Compared with SO group, the MWT and TWL of the rats in group I at each time point decreased obviously(P<0.05), the number of passes through the platform and the quadrant residence time of the platform were obviously reduced(P<0.05), and the expression of IL-6 in hippocampus CA1 was obviously increased(P<0.05).Compared with I group, the time point of MWT and TWL after operation in P group was significantly increased(P<0.05), the number of passes through the platform and the quadrant residence time of the platform were obviously increased(P<0.05) and the expression of IL-6 in hippocampus CA1 was obviously decreased(P<0.05).Conclusion:Inflammatory pain can decline spatial memory function in rats, and parecoxib sodium can alleviate the impairment, and the mechanism may be associated with the IL-6 expression in hippocampus CA1.