本文選題：血管性認知障礙 + 神經(jīng)炎性反應(yīng)�。� 參考：《山西醫(yī)科大學》2016年碩士論文

【摘要】：目的:1、觀察白細胞介素1受體拮抗劑(interleukin-l receptor antagonist,IL-1ra)對慢性腦低灌注(Chronic cerebral hypoperfusion,CCH)大鼠的認知功能(如空間學習及記憶)、海馬組織CA1區(qū)炎性細胞因子IL-1β、犬尿氨酸通路中IDO含量及活性的影響;2、探討人重組IL-1ra對CCH大鼠的認知保護作用及其機制。方法:健康雄性Spraue Dawley大鼠36只,體重(170-200)g,隨機分為假手術(shù)組、CCH模型組、CCH+IL-1ra組,每組12只。后兩組大鼠的CCH模型采用改良的頸總動脈(雙側(cè))永久性結(jié)扎。術(shù)后IL-1ra組大鼠給予側(cè)腦室注射人重組IL-1ra(10μL/只/天),假手術(shù)組及CCH模型組大鼠同時給予等量的生理鹽水注射。大鼠認知功能的評價主要采用Morris水迷宮。免疫組化檢測各組大鼠海馬組織CA1區(qū)IL-1β及IDO的陽性表達水平。ELASA法檢測各組大鼠海馬組織的KYN、Trp水平。結(jié)果:1、Morris水迷宮結(jié)果:(1)定位航行:訓練期第4、5天,CCH模型組大鼠的逃避潛伏期時間明顯多于假手術(shù)組(P0.05)。給予人重組IL-1ra干預(yù)的IL-1ra組大鼠在第4、5天逃避潛伏期時間均少于以上模型組(P0.05)。(2)空間探索:游泳速度差異無統(tǒng)計學意義(P0.05),表明相關(guān)手術(shù)及微注射等處理并未影響大鼠全身運動能力。CCH模型組大鼠穿越平臺位置的次數(shù)、目標象限停留時間較假手術(shù)組均明顯減少(P0.05)。與CCH模型組大鼠對比中,IL-1ra組大鼠穿越平臺位置次數(shù)、目標象限停留時間均增加(P0.05)。2、免疫組化結(jié)果:CCH模型組大鼠海馬區(qū)IL-1β、IDO陽性表達的IOD值統(tǒng)計結(jié)果分別為,均高于假手術(shù)組(P0.05);與CCH模型組大鼠比較,IL-1ra組大鼠IL-1β、IDO陽性表達均降低(P0.05)。3、ELISA法結(jié)果:CCH模型組大鼠的KYN/Trp比值較假手術(shù)組明顯升高(P0.05);與模型組比較,IL-1ra組大鼠KYN/Trp的比值明顯降低(P0.05)。結(jié)論:1、CCH大鼠的認知功能(空間學習及記憶)下降,其海馬組織中IL-1β、IDO的表達升高及IDO活性增強。2、人重組IL-1ra可以改善CCH大鼠的學習與記憶能力,減少IL-1β、IDO表達及抑制IDO活性,可能通過抗神經(jīng)炎性損傷及抑制犬尿氨酸途徑來發(fā)揮認知保護作用。
[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.
【學位授予單位】：山西醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R749.13

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