孕期乙醇暴露所致的胎鼠海馬神經(jīng)毒性作用及其對神經(jīng)元結(jié)構(gòu)和相關(guān)功能的影響
發(fā)布時間:2018-05-19 22:20
本文選題:乙醇 + 地塞米松 ; 參考:《廣東醫(yī)學(xué)》2017年10期
【摘要】:目的研究孕期乙醇暴露對胎鼠海馬神經(jīng)元結(jié)構(gòu)與相關(guān)功能的影響,并探討其可能的發(fā)生機(jī)制。方法將體重為250~300 g的Wistar大鼠,以雌∶雄=2∶1合籠,雌鼠受孕后隨機(jī)分為對照組、地塞米松組和乙醇組。孕9 d起,地塞米松組以1 mg/(kg·d)地塞米松皮下注射,乙醇組以4 g/(kg·d)乙醇灌胃,對照組給予等體積蒸餾水,連續(xù)給藥至受孕20 d。孕鼠于受孕20 d經(jīng)異氟醚麻醉后,剖宮取出胎鼠,選取胎鼠數(shù)量在8~14只的母鼠,胎鼠斷頭取血,并分離胎海馬組織,實時定量PCR技術(shù)檢測海馬相關(guān)功能的基因表達(dá)。各組取胎鼠全腦常規(guī)固定、制片,并行病理組織學(xué)(HE染色)和細(xì)胞超微結(jié)構(gòu)觀察。結(jié)果 HE染色顯示,孕期地塞米松和乙醇暴露的胎鼠海馬神經(jīng)元排列整齊、規(guī)則,與對照組比較無明顯改變;電鏡結(jié)果顯示,與對照組相比,地塞米松組和乙醇組出現(xiàn)內(nèi)質(zhì)網(wǎng)擴(kuò)張,高爾基體肥大。孕期地塞米松暴露后,雄性胎鼠胰島素樣生長因子(IGF)-1、IGF-1R、AKT2、Bcl-2及Caspase-8、SNAP25、NR2B和GLUR1、11β-HSD-1和MR的mRNA表達(dá)顯著升高(P0.05,P0.01),Bax、Cdc42、NR1和GLUR2、PKACa、11β-HSD-2和BDNF的mRNA表達(dá)顯著下降(P0.01),Bax/Bcl-2比值顯著降低(P0.01),Cyclin A、Rac、Rho A、NR2A、GLUR3和Syn1、GR、Egr-1及5HTr7表達(dá)無顯著改變。孕期乙醇暴露后,IGF-1、IGF-1R、AKT2、CDK2、Bcl-2、Caspase-8、Rac、NR1、NR2A、NR2B、Syn1、SNAP25、HCN1和HCN2、GR、MR、5HTr7及Egr-1的mRNA表達(dá)顯著升高(P0.05,P0.01),Cyclin A、Bax、Caspase 3、Cdc42、GLUR2和GLUR3、PKACa及BDNF的mRNA表達(dá)顯著降低(P0.01),Bax/Bcl-2比值顯著降低(P0.01),Rho A和GLUR1、11β-HSD-1的mRNA表達(dá)差異無統(tǒng)計學(xué)意義。結(jié)論孕期乙醇暴露在一定程度上不僅影響了胎鼠海馬神經(jīng)結(jié)構(gòu),而且海馬神經(jīng)元增殖與凋亡、學(xué)習(xí)與記憶、GC代謝與營養(yǎng)發(fā)育等相關(guān)功能發(fā)生了變化,并出現(xiàn)細(xì)胞的增殖和代謝升高的趨勢,表明海馬損傷的同時出現(xiàn)了一定的代償作用。乙醇所致的胎鼠海馬結(jié)構(gòu)和相關(guān)功能改變可能與c AMP/Egr-1/GR/BDNF通路改變有關(guān)。
[Abstract]:Objective to study the effects of alcohol exposure during pregnancy on the hippocampal neuronal structure and related functions in fetal rats and to explore its possible mechanism. Methods Wistar rats weighing 250g were randomly divided into control group, dexamethasone group and ethanol group with female: male 2: 1 cage. From the 9th day of pregnancy, the dexamethasone group was subcutaneously injected with dexamethasone 1 mg/(kg d, the ethanol group was given 4 g/(kg d) ethanol, and the control group was given the same volume distilled water until 20 days of pregnancy. The pregnant rats were anesthetized by isoflurane on the 20th day of pregnancy. The fetal rats were taken out from the uterus, and the fetal rats with 814 fetal rats were selected. The fetal hippocampus was isolated and the fetal hippocampal tissues were isolated. The expression of genes related to hippocampal function was detected by real-time quantitative PCR technique. Fetal rats in each group were treated with routine brain fixation, radiography, HE staining and ultrastructure observation. Results HE staining showed that the hippocampal neurons of fetal rats exposed to dexamethasone and ethanol during pregnancy were arranged neatly and regular, but there was no obvious change compared with the control group. Endoplasmic reticulum dilation and Golgi body hypertrophy appeared in dexamethasone group and ethanol group. 瀛曟湡鍦板綾蟲澗鏆撮湶鍚,
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