發(fā)布時(shí)間：2018-11-27 14:10

【摘要】：[目的]探討鉛(Pb)暴露對(duì)快速衰老小鼠(SAMP8)學(xué)習(xí)記憶能力的影響及其機(jī)制。[方法]雄性SAMP8小鼠及其野生型SAMR1小鼠各20只,各隨機(jī)分為2組,即SAMR1組、SAMR1+Pb組和SAMP8組、SAMP8+Pb組。SAMR1+Pb組和SAMP8+Pb組小鼠每天飼以0.05 g/L醋酸鉛飲用水,SAMR1組和SAMP8組小鼠每天飼以0.05 g/L醋酸鈉飲用水,共飲水9周。應(yīng)用Morris水迷宮實(shí)驗(yàn)檢測(cè)小鼠學(xué)習(xí)記憶能力;采用免疫熒光法測(cè)定實(shí)驗(yàn)小鼠側(cè)腦室下區(qū)(SVZ)淀粉樣前體蛋白(APP)、神經(jīng)元母細(xì)胞和星形膠質(zhì)樣細(xì)胞特異性標(biāo)志物[雙皮質(zhì)素(DCX)、神經(jīng)膠質(zhì)纖維酸性蛋白(GFAP)]的表達(dá)情況,分析神經(jīng)元母細(xì)胞和星形膠質(zhì)細(xì)胞的細(xì)胞比率變化;應(yīng)用實(shí)時(shí)熒光定量PCR檢測(cè)實(shí)驗(yàn)小鼠SVZ中DCX、GFAP和腦源性神經(jīng)營(yíng)養(yǎng)因子(BDNF)的m RNA表達(dá)情況。[結(jié)果]小鼠Morris水迷宮實(shí)驗(yàn)第3天結(jié)果顯示:與SAMR1組[(10.94±3.98)s]相比,SAMP8組[(29.24±6.15)s]、SAMR1+Pb組[(34.15±6.78)s]和SAMP8+Pb組[(50.86±8.56)s]的逃避潛伏期延長(zhǎng),差異有統(tǒng)計(jì)學(xué)意義(P0.05);且與SAMP8組和SAMR1+Pb組小鼠比較,SAMP8+Pb組小鼠的逃避潛伏期更長(zhǎng)(P0.05)。SAMR1組、SAMP8組、SAMR1+Pb組和SAMP8+Pb組小鼠的平均穿越平臺(tái)次數(shù)分別為(6.75±1.28)、(3.25±1.28)、(3.88±1.46)、(1.25±0.46)次;SAMP8組、SAMR1+Pb組和SAMP8+Pb組小鼠穿越次數(shù)較SAMR1組均減少(P0.05);SAMP8+Pb組小鼠穿越次數(shù)也明顯低于SAMP8組和SAMR1+Pb組(P0.05)。免疫熒光法測(cè)定結(jié)果顯示:與SAMR1組小鼠比較,SAMR1+Pb組、SAMP8組和SAMP8+Pb組小鼠SVZ區(qū)APP熒光強(qiáng)度分別上升了79%、53%和216%;與SAMR1+Pb組和SAMP8組比較,SAMP8+Pb組小鼠APP熒光強(qiáng)度分別上升了76%和107%,差異均具有統(tǒng)計(jì)學(xué)意義(P0.05)。與SAMR1組小鼠比較,SAMP8組和SAMP8+Pb組小鼠SVZ中GFAP(+)/DAPI(+)和DCX(+)/DAPI(+)細(xì)胞比率均降低,SAMP8+Pb組小鼠SVZ的GFAP(+)/DAPI(+)和DCX(+)/DAPI(+)細(xì)胞比率分別為SAMP8組小鼠的22%和59%。實(shí)時(shí)熒光定量PCR分析結(jié)果顯示:與SAMR1組小鼠相比,SAMR1+Pb組、SAMP8組和SAMP8+Pb組小鼠SVZ中BDNF和DCX m RNA表達(dá)明顯下降(P0.05);SAMP8+Pb組小鼠BDNF m RNA表達(dá)較SAMR1+Pb組和SAMP8組小鼠分別下降了85%和83%,DCX mR NA表達(dá)則分別下降了81%和60%,差異有統(tǒng)計(jì)學(xué)意義(P0.05);SAMP8組和SAMP8+Pb組小鼠的GFAP m RNA表達(dá)較SAMR1組明顯下降,并且SAMP8+Pb組小鼠GFAP m RNA表達(dá)較SAMR1+Pb組和SAMP8組分別下降了89%和69%,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。[結(jié)論]鉛暴露可導(dǎo)致快速衰老小鼠SVZ中APP表達(dá)增加和BDNF m RNA表達(dá)下降,同時(shí)加劇SVZ中星形膠質(zhì)樣細(xì)胞丟失,逃避潛伏期延長(zhǎng),穿臺(tái)次數(shù)下降,提示鉛暴露加劇快速衰老小鼠學(xué)習(xí)記憶能力的下降。
[Abstract]:[objective] to investigate the effect of lead (Pb) exposure on learning and memory ability of rapid aging mice (SAMP8) and its mechanism. [methods] Twenty male SAMP8 mice and their wild-type SAMR1 mice were randomly divided into two groups: SAMR1 group, SAMR1 Pb group and SAMP8 group, SAMP8 Pb group, SAMR1 Pb group and SAMP8 Pb group. Mice in SAMR1 group and SAMP8 group were fed with 0.05 g / L sodium acetate drinking water daily for 9 weeks. Morris water maze test was used to detect the ability of learning and memory in mice. Detection of specific markers of (SVZ) amyloid precursor protein (APP),) neuron mother cells and astrocytes in subventricular region of mice by immunofluorescence assay The expression of glial fibrillary acidic protein (GFAP) and the ratio of neuron mother cells and astrocytes were analyzed. The expression of DCX,GFAP and brain-derived neurotrophic factor (BDNF) m RNA in SVZ of experimental mice was detected by real-time fluorescence quantitative PCR. [results] on the 3rd day of Morris water maze test in mice, the results showed that compared with SAMR1 group [(10.94 鹵3.98) s], SAMP8 group [(29.24 鹵6.15) s], The escape latency of SAMR1 Pb group [(34.15 鹵6.78) s] and SAMP8 Pb group [(50.86 鹵8.56) s] was prolonged (P0.05). The escape latency of SAMP8 Pb group was longer than that of SAMP8 group and SAMR1 Pb group (P0.05). The average crossing times of SAMR1 group, SAMP8 group, SAMR1 Pb group and SAMP8 Pb group were (6.75 鹵1.28), (3.25 鹵1.28, respectively. (3. 88 鹵1. 46), (1. 25 鹵0. 46) times; The crossing times of SAMP8 group, SAMR1 Pb group and SAMP8 Pb group were significantly lower than those of SAMR1 group (P0.05), and that of SAMP8 Pb group was significantly lower than that of SAMP8 group and SAMR1 Pb group (P0.05). Compared with SAMR1 group, the fluorescence intensity of APP in SVZ region of SAMR1 Pb group, SAMP8 group and SAMP8 Pb group increased by 79% and 216%, respectively. Compared with SAMR1 Pb group and SAMP8 group, the fluorescence intensity of APP in SAMP8 Pb group increased by 76% and 107%, respectively, and the difference was statistically significant (P0.05). Compared with SAMR1 group, the ratio of GFAP () / DAPI () and DCX () / DAPI () cells in SVZ of SAMP8 group and SAMP8 Pb group decreased. The GFAP () / DAPI () and DCX () / DAPI () ratios of SVZ in SAMP8 Pb group were 22% and 59% of those in SAMP8 group, respectively. The results of real-time fluorescence quantitative PCR analysis showed that the expression of BDNF and DCX m RNA in SVZ of SAMR1 Pb group, SAMP8 group and SAMP8 Pb group was significantly lower than that of SAMR1 group (P0.05). Compared with SAMR1 Pb group and SAMP8 group, the expression of BDNF m RNA in SAMP8 Pb group decreased by 85% and 83%, and decreased by 81% and 60%, respectively (P0.05). The expression of GFAP m RNA in SAMP8 group and SAMP8 Pb group was significantly lower than that in SAMR1 group, and the GFAP m RNA expression in SAMP8 Pb group was 89% and 69% lower than that in SAMR1 Pb group and SAMP8 group, respectively. The difference was statistically significant (P0.05). [conclusion] lead exposure can increase the expression of APP and decrease the expression of BDNF m RNA in SVZ of rapidly aging mice, and aggravate the loss of astrocytes in SVZ, prolong the escape latency and decrease the number of platform penetration. It suggested that lead exposure aggravated the decline of learning and memory ability in rapidly aging mice.
【作者單位】： 華北理工大學(xué)公共衛(wèi)生學(xué)院;華北理工大學(xué)醫(yī)學(xué)實(shí)驗(yàn)動(dòng)物中心;
【基金】：國(guó)家自然科學(xué)基金項(xiàng)目(編號(hào):81373033,81673208)
【分類(lèi)號(hào)】：R114

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本文編號(hào)：2361062