【摘要】：目的研究重復(fù)sc給予丙烯酰胺(AM)28 d后對(duì)學(xué)習(xí)記憶的影響及其可能的作用機(jī)制,以及單次sc給予AM后對(duì)大鼠海馬高頻刺激后群峰電位(PS)幅度改變的影響。方法雌性Wistar大鼠分別sc給予AM 10,20和40 mg·kg-1(給藥當(dāng)天計(jì)為第1天),連續(xù)給予28 d。每周記錄1次體質(zhì)量。于第22~第27天進(jìn)行Morris水迷宮實(shí)驗(yàn),評(píng)價(jià)AM對(duì)大鼠空間定位能力的影響;分別于第29和第30天進(jìn)行跳臺(tái)實(shí)驗(yàn),觀察5 min內(nèi)大鼠跳下平臺(tái)的次數(shù)以及首次跳下平臺(tái)的時(shí)間。取AM 40 mg·kg-1組大鼠海馬組織,Western蛋白印跡法檢測(cè)N-甲基-D-天冬氨酸受體(NR)2A及2B與Ⅱ型鈣調(diào)蛋白激酶(Ca MKⅡ)的表達(dá)與磷酸化水平。另取Wistar雌性大鼠,單次sc給予AM 40 mg·kg-1,進(jìn)行長(zhǎng)時(shí)程增強(qiáng)(LTP)實(shí)驗(yàn),觀察高頻刺激后PS的改變。結(jié)果與正常對(duì)照組相比,給予AM后,大鼠體質(zhì)量增長(zhǎng)減緩(P0.01)。AM 20及40 mg·kg-1組大鼠找到平臺(tái)的時(shí)間顯著延長(zhǎng),但是對(duì)大鼠穿越平臺(tái)的次數(shù)無(wú)顯著影響。與實(shí)驗(yàn)首日(第29天)相比,經(jīng)過(guò)電擊強(qiáng)化學(xué)習(xí)記憶,正常對(duì)照組大鼠為躲避電擊,次日(第30天)5 min內(nèi)跳下平臺(tái)的次數(shù)顯著減少(P0.01),且首次跳下平臺(tái)的時(shí)間明顯延長(zhǎng)(P0.01),而AM 10,20和40 mg·kg-1組5 min內(nèi)的錯(cuò)誤次數(shù)以及首次跳下平臺(tái)的時(shí)間無(wú)顯著改變。Western蛋白印跡結(jié)果顯示,與正常對(duì)照組相比,AM 40 mg·kg-1組大鼠海馬組織中NR2A及NR2B的表達(dá)與磷酸化水平顯著增加,且Ca MKⅡ磷酸化水平顯著升高(P0.01)。LTP結(jié)果顯示,與正常對(duì)照組相比,單次sc給予AM 40 mg·kg-1顯著降低Wistar雌性大鼠海馬的PS幅度(P0.01),損傷了大鼠海馬部位的突觸可塑性。結(jié)論 AM可能通過(guò)改變谷氨酸的含量,增加NR的表達(dá)與活性,導(dǎo)致鈣超載,引發(fā)神經(jīng)細(xì)胞死亡,從而使LTP的PS幅度下降,影響海馬神經(jīng)突觸的可塑性,最終影響中樞的學(xué)習(xí)記憶功能。
[Abstract]:Objective to study the effects of repeated acrylacrylamide (AM) on learning and memory and its possible mechanism, and the effects of single sc administration of AM on the changes of (PS) amplitude of group potential after high-frequency stimulation in hippocampus of rats. Methods female Wistar rats were given AM1020 and 40 mg kg-1 (day 1) for 28 days, respectively. Body mass was recorded once a week. The Morris water maze test was carried out from 22 to 27 days to evaluate the influence of AM on the spatial positioning ability of rats, and the platform jumping experiments were carried out on the 29th and 30th days, respectively, to observe the times of jumping off the platform and the time of the first jumping from the platform within 5 min. The expression and phosphorylation of N-methyl-Daspartate receptor (NR) 2A), calmodulin kinase type 2B (2B) and calmodulin kinase 鈪，

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