孕期尼古丁暴露致大鼠胎肾上腺载脂蛋白表达改变及发育毒性
发布时间:2018-05-06 03:42
本文选题:尼古丁 + 载脂蛋白 ; 参考:《中国医院药学杂志》2015年08期
【摘要】:目的:研究孕期尼古丁暴露对胎肾上腺相关载脂蛋白(apolipoprotein,Apo)基因表达水平的影响,揭示其对胎肾上腺发育的直接毒性作用及可能机制。方法:健康Wistar雌性大鼠受孕后第7~17天起早晚各一次sc给予尼古丁1.0 mg·kg-1或等量生理盐水,孕第17天处死,记录胎鼠体质量、身长、胎盘质量,计算宫内发育迟缓(intrauterine growth retardation,IUGR)发生率。收集胎肾上腺用于透射电镜、全基因组表达谱芯片及荧光实时定量反转录PCR(reverse-transcription PCR,RT-PCR)检测。结果:与正常对照组相比,尼古丁暴露组胎鼠体质量、身长降低(P0.01,P0.05),胎盘质量降低(P0.01),IUGR发生率升高(P0.01);透射电镜结果显示胎肾上腺皮质细胞表现出线粒体水肿、胞浆内空泡等现象;全基因组表达谱芯片结果显示,胎肾上腺各类Apo基因中载脂蛋白B型(apolipoprotein B,ApoB)与载脂蛋白C型Ⅱ类(apolipoprotein C-Ⅱ,ApoC-Ⅱ)的表达显著降低(变化倍数≥2视为显著性变化),载脂蛋白A型Ⅰ(apolipoprotein A-Ⅰ,ApoA-Ⅰ)与载脂蛋白A型Ⅱ类(apolipoprotein A-Ⅱ,ApoA-Ⅱ)的表达变化也接近显著性水平;RT-PCR检测结果显示,ApoA-Ⅱ、ApoC-Ⅱ表达降低(P0.05,P0.05),ApoA-Ⅰ表达也呈下降趋势(P=0.12)。结论:孕期尼古丁暴露所致IUGR等不良妊娠结局,其发生机制可能与胎肾上腺相应Apo表达改变所致胆固醇转运异常,进而引起甾体激素合成受阻有关。
[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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