尼古丁对胎儿宫内发育的影响及其甾体激素合成干扰机制

发布时间：2018-01-30 14:00

本文关键词： 尼古丁宫内发育迟缓甾体激素急性调节蛋白细胞色素P侧链裂解酶　出处：《广东医学》2017年03期 　论文类型：期刊论文

【摘要】：目的探讨孕期尼古丁暴露所致胎儿宫内发育迟缓(IUGR)的甾体激素合成干扰机制。方法选用Wistar雌性和雄性大鼠,适应性喂养1周后,每晚18:00按雌∶雄=2∶1合笼,次晨检见阴栓者记为受孕0日。尼古丁组从孕8日起皮下注射尼古丁1.0 mg/kg,2次/d,给药容积为2 m L/kg,直至孕21日。对照组给予等容量的生理盐水。处死孕鼠,收集血清,摘取并冻存肾上腺和胎盘组织。剖腹取胎,记录胎盘质量、胎鼠体质量及其他发育指标,摘取并冻存孕21日胎鼠肾上腺。用放射免疫法检测孕鼠血清皮质酮、胎盘催乳素和雌三醇水平。观察胎盘组织病理学改变。用实时定量RT-PCR方法检测肾上腺St AR和P450scc、胎盘2型11β羟基类固醇脱氢酶(11β-HSD-2)、肾上腺细胞色素P450 1A1(CYP1A1)及其芳烃受体(AhR)的mRNA表达。结果从孕8日开始皮下注射尼古丁明显导致大鼠IUGR的发生(P0.01)。尼古丁使孕鼠血清皮质酮水平在孕中期及孕晚期均明显升高(P0.05)。相对于对照组,孕中期及孕晚期尼古丁组孕鼠肾上腺St AR和P450scc的mRNA表达水平显著升高(P0.05,P0.01),但是胎鼠肾上腺的St AR和P450scc的mRNA表达水平则有下降趋势(P=0.16,P=0.11)。同时,尼古丁组足月大鼠胎盘迷路区的病理形态学发生了明显的改变,包括迷路区出血和滋养层细胞变性;并使孕中、晚期反映胎盘功能的孕鼠血清胎盘催乳素水平(P0.05)、血清雌三醇水平以及胎盘11β-HSD-2的mRNA表达显著下降(P0.05)。尼古丁对母鼠肾上腺的CYP1A1和AhR的mRNA表达有一定的诱导作用,但是对胎鼠肾上腺的CYP1A1和AhR的mRNA表达没有明显影响。结论孕期接触尼古丁可明显导致IUGR的发生,且与母体及胎儿甾体激素内环境紊乱密切相关。
[Abstract]:Objective to investigate the prenatal nicotine exposure caused by intrauterine growth retardation (IUGR) steroid hormone synthesis interference mechanism. Methods Wistar male and female rats, after 1 weeks of feeding, every night 18:00 according to =2: 1 female: male mated. The next morning seized a vaginal plug for pregnancy 0 days. Nicotine group from the pregnant 8 days subcutaneous injection of nicotine for 1 mg/kg, 2 /d, dose volume 2 m L/kg, until the pregnancy for 21 days. The control group was given normal saline water. Pregnant mice were killed, serum was collected and frozen for removal of the adrenal gland and placenta. Caesarean section, placental fetal body quality, quality rats and other development indicators, the removal and freezing. At day 21 of gestation, fetal rat adrenal gland. The detection of serum corticosterone in pregnant rats by radioimmunoassay, placental lactogen and female three alcohol level. To observe pathological changes of placenta. Using real-time quantitative RT-PCR method for detection of AR and P450scc in fetal adrenal St, disc type 2 11 beta hydroxy Hydroxysteroid dehydrogenase (11 P -HSD-2), adrenal cytochrome P450 1A1 (CYP1A1) and its receptor (AhR) mRNA arene. Results the expression from pregnant 8 day subcutaneous injection of nicotine significantly resulted in IUGR rats (P0.01). The serum corticosterone levels of nicotine rats during pregnancy period and late pregnancy were significantly higher (P0.05). Compared with the control group, the expression level of mid pregnancy and late pregnancy nicotine group of pregnant rats adrenal St AR and P450scc mRNA increased significantly (P0.05, P0.01), but the AR and St fetal rat adrenal P450scc mRNA expression decreased (P=0.16, P=0.11). At the same time, nicotine group full-term rat placenta lost the pathological area changed significantly, including the lost area of bleeding and trophoblast cell degeneration; and the pregnancy in late pregnant rats serum placental function reflects placental prolactin levels (P0.05), serum levels of placenta and three female alcohol 11 beta -HSD -2 mRNA expression decreased significantly (P0.05). Nicotine on maternal adrenal CYP1A1 and AhR mRNA expression induced by some, but on fetal adrenal CYP1A1 and AhR mRNA expression had no obvious effect. Conclusion the nicotine exposure during pregnancy could lead to the occurrence of IUGR, which is closely related with the environmental disturbance of maternal and fetal steroid hormones in the body.

【作者单位】：中国人民武装警察部队广东省总队医院妇科;广东省妇幼保健院产科;中国人民武装警察部队广东省总队医院医务处;
【基金】：广东省中医药局建设中医药强省科研课题(编号:20132091)
【分类号】：R714.5
【正文快照】： 511400)胎儿宫内发育迟缓(intrauterine growth retarda-tion,IUGR)是指孕周大于37周,胎儿出生体质量小于2 500 g,或胎儿体质量低于其孕龄平均体质量第10百分位数,或低于其平均体质量的2个标准差的病理性胎儿生长受限[1]。正常妊娠人群中IUGR发生率大约为5%[2]。IUGR患儿围产

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