腦源性神經(jīng)營(yíng)養(yǎng)因子通路的抑制介導(dǎo)孕期攝食限制所致的雄性子代大鼠海馬發(fā)育損傷
發(fā)布時(shí)間:2018-02-27 23:28
本文關(guān)鍵詞: 孕期攝食限制 海馬 宮內(nèi)編程 腦源性神經(jīng)營(yíng)養(yǎng)因子 突觸可塑性 出處:《中國(guó)藥理學(xué)與毒理學(xué)雜志》2015年03期 論文類型:期刊論文
【摘要】:目的觀察孕期攝食限制(PFR)所致雄性子代鼠海馬結(jié)構(gòu)及功能損傷改變,并探討其發(fā)生機(jī)制。方法健康Wistar雌性大鼠受孕后第11~20天(GD11~GD20)限食,給予正常對(duì)照組日均攝食量的50%,部分孕鼠于GD20麻醉處死取胎鼠;其余孕鼠自然生產(chǎn)所得雄性子代鼠斷奶后給予高脂飲食喂養(yǎng),一批于生后17周齡(PW17)麻醉處死,另一批從PW17起,21 d內(nèi)給予慢性不可預(yù)知性刺激(UCS)后,于PW20處死,取海馬組織。采用HE染色和(或)透射電鏡進(jìn)行組織學(xué)觀察,ELISA試劑盒檢測(cè)胎鼠血皮質(zhì)酮水平,PCR檢測(cè)海馬糖皮質(zhì)激素受體(Gr)、腦源性神經(jīng)營(yíng)養(yǎng)因子(Bdnf)通路、突觸可塑性相關(guān)基因的mRNA表達(dá)。結(jié)果與正常對(duì)照組相比,PFR胎鼠海馬顯示亞細(xì)胞水平病理?yè)p傷,胎血皮質(zhì)酮水平增加了1.19倍(P0.05),Gr mRNA表達(dá)升高了38%(P0.05),Bdnf、N-甲基-D-天冬氨酸受體亞單位1(Nr1)、Nr2B和突觸蛋白Ⅰ的mRNA表達(dá)分別降低了25.0%,16.1%,16.1%和17.6%(P0.05)。與高脂對(duì)照組相比,PFR成年子代鼠海馬僅顯示輕微病理改變,而PFR成年子代鼠在UCS后,海馬病理?yè)p傷明顯,表現(xiàn)為錐體細(xì)胞層極薄,細(xì)胞間隙增大,細(xì)胞數(shù)目減少和核皺縮,同時(shí)海馬c AMP應(yīng)答元件結(jié)合蛋白、Bdnf、酪氨酸激酶受體及Nr1 mRNA表達(dá)分別顯著降低了51.0%,50.0%,52.0%和33.3%(P0.05,P0.01)。結(jié)論 PFR可致雄性子代鼠海馬結(jié)構(gòu)及功能損傷,其機(jī)制可能與PFR所致的母源性高GC引起子代鼠海馬Bdnf通路抑制有關(guān)。
[Abstract]:Objective to observe the changes of hippocampal structure and function in male offspring induced by dietary restriction during pregnancy, and to explore its mechanism. Methods healthy Wistar female rats were treated with GD11GD20 on the 20th day after conception. Some of the pregnant rats were anesthetized by GD20 to kill the fetuses, while the rest of the pregnant rats were fed with high-fat diet after weaning, and some of them were anesthetized and executed at the age of 17 weeks after birth. Another group received chronic unpredictable stimulation within 21 days from the onset of PW17 and then died in PW20. Using HE staining and / or transmission electron microscope (TEM) to detect serum corticosterone level in fetal rats. The glucocorticoid receptor (Gr) and brain-derived neurotrophic factor (BDNF) pathway in hippocampus were detected by PCR. The expression of synaptic plasticity related gene mRNA. Results compared with the normal control group, the hippocampus of fetal rats showed subcellular pathological damage. Fetal serum corticosterone level increased by 1.19 times P0.05Gr mRNA expression and increased the expression of mRNA of N- methyl-Daspartic acid receptor subunit N- Nr2B and synaptophysin 鈪,
本文編號(hào):1544784
本文鏈接:http://sikaile.net/yixuelunwen/mazuiyixuelunwen/1544784.html
最近更新
教材專著