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孕期尼古丁暴露致大鼠胎腎上腺載脂蛋白表達(dá)改變及發(fā)育毒性

發(fā)布時(shí)間:2018-05-06 03:42

  本文選題:尼古丁 + 載脂蛋白; 參考:《中國(guó)醫(yī)院藥學(xué)雜志》2015年08期


【摘要】:目的:研究孕期尼古丁暴露對(duì)胎腎上腺相關(guān)載脂蛋白(apolipoprotein,Apo)基因表達(dá)水平的影響,揭示其對(duì)胎腎上腺發(fā)育的直接毒性作用及可能機(jī)制。方法:健康Wistar雌性大鼠受孕后第7~17天起早晚各一次sc給予尼古丁1.0 mg·kg-1或等量生理鹽水,孕第17天處死,記錄胎鼠體質(zhì)量、身長(zhǎng)、胎盤(pán)質(zhì)量,計(jì)算宮內(nèi)發(fā)育遲緩(intrauterine growth retardation,IUGR)發(fā)生率。收集胎腎上腺用于透射電鏡、全基因組表達(dá)譜芯片及熒光實(shí)時(shí)定量反轉(zhuǎn)錄PCR(reverse-transcription PCR,RT-PCR)檢測(cè)。結(jié)果:與正常對(duì)照組相比,尼古丁暴露組胎鼠體質(zhì)量、身長(zhǎng)降低(P0.01,P0.05),胎盤(pán)質(zhì)量降低(P0.01),IUGR發(fā)生率升高(P0.01);透射電鏡結(jié)果顯示胎腎上腺皮質(zhì)細(xì)胞表現(xiàn)出線粒體水腫、胞漿內(nèi)空泡等現(xiàn)象;全基因組表達(dá)譜芯片結(jié)果顯示,胎腎上腺各類Apo基因中載脂蛋白B型(apolipoprotein B,ApoB)與載脂蛋白C型Ⅱ類(apolipoprotein C-Ⅱ,ApoC-Ⅱ)的表達(dá)顯著降低(變化倍數(shù)≥2視為顯著性變化),載脂蛋白A型Ⅰ(apolipoprotein A-Ⅰ,ApoA-Ⅰ)與載脂蛋白A型Ⅱ類(apolipoprotein A-Ⅱ,ApoA-Ⅱ)的表達(dá)變化也接近顯著性水平;RT-PCR檢測(cè)結(jié)果顯示,ApoA-Ⅱ、ApoC-Ⅱ表達(dá)降低(P0.05,P0.05),ApoA-Ⅰ表達(dá)也呈下降趨勢(shì)(P=0.12)。結(jié)論:孕期尼古丁暴露所致IUGR等不良妊娠結(jié)局,其發(fā)生機(jī)制可能與胎腎上腺相應(yīng)Apo表達(dá)改變所致膽固醇轉(zhuǎn)運(yùn)異常,進(jìn)而引起甾體激素合成受阻有關(guān)。
[Abstract]:Aim: to study the effect of nicotine exposure during pregnancy on the expression of apolipoprotein protein (ApoP) gene in fetal adrenal gland, and to reveal its direct toxic effect on the development of fetal adrenal gland and its possible mechanism. Methods: healthy Wistar female rats were given nicotine 1.0 mg kg-1 or the same amount of normal saline once in the morning and evening from 7 to 17 days after conception. The fetal weight, body length and placental mass were recorded on the 17th day of pregnancy. The incidence of intrauterine growth retardation growth retard was calculated. Fetal adrenal glands were collected for transmission electron microscopy (TEM), genome-wide expression microarray and real-time quantitative reverse transcription-polymerase chain reaction (PCR(reverse-transcription) RT-PCR. Results: compared with the normal control group, the fetal body weight, body length and placental weight decreased in the nicotine exposure group, and the incidence of IUGR in the placental decreased group was higher than that in the control group, and transmission electron microscope showed that the fetal adrenal cortical cells showed mitochondrial edema and cytosolic vacuolation. The whole genome expression microarray showed that, The expression of apolipoprotein B (ApoB) and apolipoprotein C- 鈪,

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