【摘要】：目的評(píng)估阿司匹林(aspirin)通過抑制腦內(nèi)炎癥反應(yīng)對(duì)顳葉癲癇(TLE)慢性期小鼠空間學(xué)習(xí)記憶能力的影響,并從海馬神經(jīng)再生角度初探其機(jī)制。方法匹魯卡品(pilocarpine)制作小鼠TLE模型,在慢性期分別腹腔注射不同劑量阿司匹林(20、60、80mg/kg)或同體積生理鹽水,用Western blot和ELISA檢測(cè)海馬環(huán)氧化物酶-2(COX-2)和前列腺素E2(PGE2)變化,Morris水迷宮實(shí)驗(yàn)評(píng)估動(dòng)物的空間學(xué)習(xí)記憶能力并觀察海馬神經(jīng)元C-fos表達(dá)變化,BrdU+C-fos免疫熒光雙標(biāo)染色觀察齒狀回新生細(xì)胞的功能整合。重復(fù)測(cè)量(repeated measures)ANOVA比較各組水迷宮潛伏期,One-way ANOVA方法分析各組染色陽性細(xì)胞計(jì)數(shù)結(jié)果。結(jié)果腹腔注射60、80mg/kg阿司匹林可以明顯降低海馬COX-2和PGE2的表達(dá)(P0.01)。與正常同齡對(duì)照組比較,TLE慢性期動(dòng)物在Morris水迷宮任務(wù)中的表現(xiàn)明顯下降,而與生理鹽水注射模型組比較,阿司匹林治療組明顯縮短了定位航行實(shí)驗(yàn)第3~5天的潛伏期并提高了空間探索實(shí)驗(yàn)中穿越目的象限的時(shí)間比例(P0.01)。BrdU+C-fos免疫熒光染色結(jié)果顯示阿司匹林組動(dòng)物齒狀回雙標(biāo)細(xì)胞數(shù)量較生理鹽水注射組明顯增多(P0.01)。結(jié)論阿司匹林可以改善TLE慢性期小鼠空間記憶能力。通過抑制腦內(nèi)炎癥反應(yīng)、改善齒狀回微環(huán)境,促進(jìn)海馬功能性神經(jīng)再生可能是阿司匹林的治療作用機(jī)制之一。
[Abstract]:Objective to evaluate the effect of aspirin (aspirin) on spatial learning and memory in (TLE) mice with temporal lobe epilepsy by inhibiting inflammatory response in the brain, and to explore its mechanism from the perspective of hippocampal nerve regeneration. Methods the TLE model of mice was induced by pilocarpine (pilocarpine). At the chronic stage, different doses of aspirin (2060 mg / kg) or saline of the same volume were injected intraperitoneally. Western blot and ELISA were used to detect the changes of COX-2 and PGE2 in hippocampus. Morris water maze test was used to evaluate the ability of spatial learning and memory and to observe the expression of C-fos in hippocampal neurons. The functional integration of nascent cells in dentate gyrus was observed by BrdU C-fos double immunofluorescence staining. The latency of water labyrinth in each group was compared by repeated measurement of (repeated measures) ANOVA, and the count of positive cells in each group was analyzed by One-way ANOVA method. Results the expression of COX-2 and PGE2 in hippocampus was significantly decreased by intraperitoneal injection of aspirin (60 mg / kg) (P0.01). Compared with the normal control group, the performance of Morris water labyrinth was significantly decreased in the chronic phase of TLE, while that in the saline injection model group was significantly lower than that in the normal saline injection group. Aspirin treatment group significantly shortened the latency of the 3rd day of the navigation experiment and increased the proportion of time passing through the target quadrant in the space exploration experiment (P0.01). BrdU C-fos immunofluorescence staining results showed that aspirin was used in the experiment. The number of double labeled cells in dentate gyrus in forest group was significantly higher than that in saline injection group (P0.01). Conclusion Aspirin can improve the spatial memory ability of chronic TLE mice. Inhibiting inflammation in brain, improving microenvironment of dentate gyrus and promoting functional nerve regeneration in hippocampus may be one of the therapeutic mechanisms of aspirin.
【作者單位】： 西安交通大學(xué)醫(yī)學(xué)部基礎(chǔ)醫(yī)學(xué)院神經(jīng)生物學(xué)研究所;西安交通大學(xué)醫(yī)學(xué)部基礎(chǔ)醫(yī)學(xué)院人體解剖與組織胚胎學(xué)系;
【基金】：國家自然科學(xué)基金面上項(xiàng)目資助(No.81171232,81371427)~~
【分類號(hào)】：R965

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