發(fā)布時(shí)間：2018-05-17 01:00

  本文選題：孕期 + 缺氧��； 參考：《蘇州大學(xué)》2016年碩士論文

【摘要】：第一部分孕期缺氧對(duì)青年子代腦發(fā)育及學(xué)習(xí)記憶等認(rèn)知功能的影響目的:孕期缺氧可以導(dǎo)致胎兒出生后以至于成年時(shí)期出現(xiàn)各種生理病理的改變,對(duì)某些成人疾病(Adult diseases)或慢性疾病的易感性增加。本研究探討孕期缺氧對(duì)胚胎期以及青年子代腦發(fā)育及功能的長(zhǎng)期影響。方法:采用本實(shí)驗(yàn)室已建立成熟的孕期缺氧模型,將懷孕母鼠隨機(jī)分為孕期缺氧組(缺氧組,PH)和常氧組(對(duì)照組,Con)。孕期缺氧組母鼠(妊娠第4-21天)放置于10.5%缺氧箱中,對(duì)照組母鼠(妊娠第4-21天)放置于21%常氧箱中,出生后子代鼠均在常氧環(huán)境下飼養(yǎng)。分別稱量胎鼠、6周齡大鼠的體重、腦重。采用Morris水迷宮實(shí)驗(yàn)檢測(cè)6周齡子代大鼠的空間學(xué)習(xí)記憶能力。結(jié)果:孕期缺氧組胎鼠腦重及體重均明顯低于常氧對(duì)照組;孕期缺氧組6周齡子代大鼠腦重明顯低于常氧對(duì)照組,而體重并無(wú)明顯差異。Morris水迷宮實(shí)驗(yàn)結(jié)果顯示,兩組6周齡子代大鼠之間游泳速度無(wú)明顯差異,孕期缺氧子代大鼠在定位航行實(shí)驗(yàn)中需要更長(zhǎng)的時(shí)間才能找到平臺(tái);在空間搜索實(shí)驗(yàn)中的穿越平臺(tái)次數(shù)明顯低于常氧對(duì)照組。結(jié)論:孕期缺氧不僅直接影響胎兒的生長(zhǎng)和腦發(fā)育,而且其產(chǎn)生的不良效應(yīng)可持續(xù)到子代青年期,導(dǎo)致青年子代學(xué)習(xí)記憶等認(rèn)知能力下降。第二部分孕期缺氧對(duì)青年子代海馬NMDAR-Wnt-Catenin通路的影響目的:通過(guò)分子生物學(xué)手段,研究孕期缺氧對(duì)子代海馬NMDAR-Wnt-Catenin通路的影響。方法:孕期缺氧模型的建立同第一部分;取6周齡子代大鼠的新鮮海馬組織,以熒光定量PCR、Western blot方法檢測(cè)海馬組織內(nèi)NMDAR-Wnt-Catenin通路相關(guān)基因(Grin1、Grin2a、Grin2b、Wnt2、Wnt3a、Wnt5a、Wnt7a、β-catenin、Fosl1)及蛋白(NR1、NR2A、NR2B、β-catenin、活化的β-catenin)的表達(dá)。結(jié)果:熒光定量PCR結(jié)果顯示,與對(duì)照組相比,缺氧組6周齡子代大鼠海馬NMDAR相關(guān)基因Grin1、Grin2a、Grin2b均下降,其中以Grin2a下降最為明顯;Wnt通路相關(guān)基因Wnt3a明顯下降,但Wnt通路主要受體Fzd4以及LRP5/6無(wú)明顯變化、β-catenin有下降趨勢(shì)、β-catenin的下游基因Fosl1明顯下降。Western blot結(jié)果顯示,缺氧組6周齡子代鼠海馬組織內(nèi)的NR1、NR2A、NR2B、活化的β-catenin的蛋白表達(dá)量均顯著低于對(duì)照組,總的β-catenin的蛋白表達(dá)無(wú)明顯變化。結(jié)論:孕期缺氧對(duì)子代神經(jīng)系統(tǒng)產(chǎn)生長(zhǎng)期不良影響,可通過(guò)引起子代海馬組織中NMDARs以及Wnt-β-Catenin通路以及下游相關(guān)基因的改變導(dǎo)致青年子代的學(xué)習(xí)記憶等認(rèn)知功能受損。
[Abstract]:Part one the effect of hypoxia during pregnancy on the cognitive function of brain development, learning and memory of young offspring: hypoxia during pregnancy may lead to various physiological and pathological changes after birth and even in adulthood. Increased susceptibility to certain adult or chronic diseases. The aim of this study was to investigate the long-term effects of hypoxia during pregnancy on brain development and function in embryonic and young offspring. Methods: a mature model of hypoxia during pregnancy was established in our laboratory. Pregnant rats were randomly divided into two groups: hypoxia group (PHH) and normoxic group (control group). The pregnant rats of hypoxia group (4-21 days of pregnancy) were placed in 10.5% hypoxia box, the control group (4-21 days of pregnancy) were placed in 21% normoxic box, and the offspring of postnatal mice were raised in normoxic environment. The body weight and brain weight of 6 weeks old rats were measured respectively. The spatial learning and memory abilities of 6-week-old rats were measured by Morris water maze test. Results: the brain weight and body weight of fetal rats in hypoxia group were significantly lower than those in normoxic control group, and the brain weight in 6-week-old offspring in hypoxia group was significantly lower than that in normoxic control group, but there was no significant difference in body weight. Morris water maze test showed that there was no significant difference between the two groups. There was no significant difference in swimming speed between the two groups of 6-week-old rats. It took a longer time for the hypoxic offspring to find the platform in the navigation experiment, and the frequency of crossing the platform in the spatial search experiment was significantly lower than that in the normoxic control group. Conclusion: hypoxia during pregnancy can not only directly affect the growth and brain development of the fetus, but also produce adverse effects that can be sustained into the youth of the offspring, resulting in the decline of cognitive ability such as learning and memory in the young offspring. Part two effects of hypoxia during pregnancy on NMDAR-Wnt-Catenin pathway in hippocampus of young offspring objective: to study the effect of hypoxia during pregnancy on NMDAR-Wnt-Catenin pathway in hippocampus of young offspring by molecular biology. Methods: the model of anoxia during pregnancy was established in the same part, the fresh hippocampal tissues of 6-week-old rats were collected, and the expression of NMDAR-Wnt-Catenin pathway related genes, Wnt3a1, Wnt5aWnt7a, 尾 -catenininFosl1) and the protein NR1, NR2ANR2B, 尾 -catenin, activated 尾 -catenin, were detected by fluorescence quantitative blot method in hippocampal tissues. The expression of the NMDAR-Wnt-Catenin pathway related genes of Wnt3a1 and Wnt5aWnt7a, 尾 -catenin1) and the protein NR1, NR2ANR2B, 尾 -catenin, activated 尾 -catenin in hippocampal tissues were detected by fluorescence quantitative blot. Results: compared with the control group, the NMDAR related gene Grin1 and Grin2a Grin2b in the hippocampus of the anoxic group were all decreased, and the decrease of Grin2a was the most obvious. However, Fzd4 and LRP5/6, the main receptors of Wnt pathway, did not change, but 尾 -catenin gene Fosl1 decreased significantly. Western blot results showed that the expression of NR1, NR2ANR2B and activated 尾 -catenin protein in hippocampal tissues of 6-week-old filial generation rats in hypoxia group was significantly lower than that in control group. The protein expression of total 尾-catenin did not change significantly. Conclusion: hypoxia during pregnancy has a long-term adverse effect on the nervous system of the offspring, which can result in the impairment of cognitive function such as learning and memory in the young offspring by causing the changes of NMDARs, Wnt- 尾 -Catenin pathway and downstream genes in the hippocampus of the offspring.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類(lèi)號(hào)】：R714.2

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本文編號(hào)：1899181