白细胞介素1受体拮抗剂对慢性脑低灌注大鼠的认知保护作用及机制研究

发布时间：2018-05-15 05:36

本文选题：血管性认知障碍 + 神经炎性反应　；参考：《山西医科大学》2016年硕士论文

【摘要】：目的:1、观察白细胞介素1受体拮抗剂(interleukin-l receptor antagonist,IL-1ra)对慢性脑低灌注(Chronic cerebral hypoperfusion,CCH)大鼠的认知功能(如空间学习及记忆)、海马组织CA1区炎性细胞因子IL-1β、犬尿氨酸通路中IDO含量及活性的影响;2、探讨人重组IL-1ra对CCH大鼠的认知保护作用及其机制。方法:健康雄性Spraue Dawley大鼠36只,体重(170-200)g,随机分为假手术组、CCH模型组、CCH+IL-1ra组,每组12只。后两组大鼠的CCH模型采用改良的颈总动脉(双侧)永久性结扎。术后IL-1ra组大鼠给予侧脑室注射人重组IL-1ra(10μL/只/天),假手术组及CCH模型组大鼠同时给予等量的生理盐水注射。大鼠认知功能的评价主要采用Morris水迷宫。免疫组化检测各组大鼠海马组织CA1区IL-1β及IDO的阳性表达水平。ELASA法检测各组大鼠海马组织的KYN、Trp水平。结果:1、Morris水迷宫结果:(1)定位航行:训练期第4、5天,CCH模型组大鼠的逃避潜伏期时间明显多于假手术组(P0.05)。给予人重组IL-1ra干预的IL-1ra组大鼠在第4、5天逃避潜伏期时间均少于以上模型组(P0.05)。(2)空间探索:游泳速度差异无统计学意义(P0.05),表明相关手术及微注射等处理并未影响大鼠全身运动能力。CCH模型组大鼠穿越平台位置的次数、目标象限停留时间较假手术组均明显减少(P0.05)。与CCH模型组大鼠对比中,IL-1ra组大鼠穿越平台位置次数、目标象限停留时间均增加(P0.05)。2、免疫组化结果:CCH模型组大鼠海马区IL-1β、IDO阳性表达的IOD值统计结果分别为,均高于假手术组(P0.05);与CCH模型组大鼠比较,IL-1ra组大鼠IL-1β、IDO阳性表达均降低(P0.05)。3、ELISA法结果:CCH模型组大鼠的KYN/Trp比值较假手术组明显升高(P0.05);与模型组比较,IL-1ra组大鼠KYN/Trp的比值明显降低(P0.05)。结论:1、CCH大鼠的认知功能(空间学习及记忆)下降,其海马组织中IL-1β、IDO的表达升高及IDO活性增强。2、人重组IL-1ra可以改善CCH大鼠的学习与记忆能力,减少IL-1β、IDO表达及抑制IDO活性,可能通过抗神经炎性损伤及抑制犬尿氨酸途径来发挥认知保护作用。
[Abstract]:Objective to observe the effects of interleukin-l receptor antagonist IL-1raon on cognitive function (such as spatial learning and memory, IL-1 尾, CA1 inflammatory cytokine IL-1 尾, IDO content in canine uremic acid pathway) in rats with chronic cerebral hypoperfusion (CCH). To investigate the cognitive protective effect of human recombinant IL-1ra on CCH rats and its mechanism. Methods: 36 healthy male Spraue Dawley rats, weighing 170-200 g, were randomly divided into sham-operated group (CCH model group) and CCH IL-1ra group (n = 12 in each group). The CCH model of the latter two groups was permanently ligated with modified common carotid artery (bilateral). After operation, rats in IL-1ra group were given intraventricular injection of recombinant IL-1ra(10 渭 L / rat / rat, and rats in sham-operation group and CCH model group were injected with the same amount of normal saline at the same time. Morris water maze was used to evaluate the cognitive function of rats. The expression of IL-1 尾 and IDO in hippocampal tissue of rats in each group was detected by immunohistochemical method. The level of KYN TRP in hippocampal tissue of rats in each group was detected by ELASA method. Results the time of escape latency in CCH model group was significantly longer than that in sham operation group (P 0.05). The escape latency of rats in the IL-1ra group treated with human recombinant IL-1ra on the 4th day was less than that in the model group on the 4th day. (2) Spatial exploration: there was no significant difference in swimming speed (P 0.05), which indicated that the related operation and microinjection did not affect the rats. The number of times the rats in CCH model group crossed the platform position, Compared with the sham operation group, the target quadrant residence time decreased significantly (P 0.05). Compared with the rats of CCH model group, the times of crossing the platform position and the residence time of target quadrant in the IL-1ra group increased P0.05. 2. The IOD values of the positive expression of IL-1 尾 -ido in hippocampus of the rats in the control group were as follows: the immunohistochemical results were as follows: (1) the positive expression of IL-1 尾 -IDO in the hippocampus of the rats in the control group was compared with that in the control group. Compared with the model group, the positive expression of IL-1 尾 -ido in IL-1ra group was significantly lower than that in the sham operation group, and the ratio of KYN/Trp in the control group was significantly higher than that in the sham operation group, and the ratio of KYN/Trp in the IL-1ra group was significantly lower than that in the model group. Conclusion the cognitive function (spatial learning and memory) of rats with CCH was decreased, and the expression of IL-1 尾 -ido and the activity of IDO were increased. The recombinant IL-1ra could improve the learning and memory ability of CCH rats, decrease the expression of IL-1 尾 -ido and inhibit the activity of IDO. It may play a cognitive protective role through anti-neuritis injury and inhibition of canine uric acid pathway.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R749.13

【相似文献】