尼古丁對胎兒宮內(nèi)發(fā)育的影響及其甾體激素合成干擾機制
本文關(guān)鍵詞: 尼古丁 宮內(nèi)發(fā)育遲緩 甾體激素急性調(diào)節(jié)蛋白 細(xì)胞色素P側(cè)鏈裂解酶 出處:《廣東醫(yī)學(xué)》2017年03期 論文類型:期刊論文
【摘要】:目的探討孕期尼古丁暴露所致胎兒宮內(nèi)發(fā)育遲緩(IUGR)的甾體激素合成干擾機制。方法選用Wistar雌性和雄性大鼠,適應(yīng)性喂養(yǎng)1周后,每晚18:00按雌∶雄=2∶1合籠,次晨檢見陰栓者記為受孕0日。尼古丁組從孕8日起皮下注射尼古丁1.0 mg/kg,2次/d,給藥容積為2 m L/kg,直至孕21日。對照組給予等容量的生理鹽水。處死孕鼠,收集血清,摘取并凍存腎上腺和胎盤組織。剖腹取胎,記錄胎盤質(zhì)量、胎鼠體質(zhì)量及其他發(fā)育指標(biāo),摘取并凍存孕21日胎鼠腎上腺。用放射免疫法檢測孕鼠血清皮質(zhì)酮、胎盤催乳素和雌三醇水平。觀察胎盤組織病理學(xué)改變。用實時定量RT-PCR方法檢測腎上腺St AR和P450scc、胎盤2型11β羥基類固醇脫氫酶(11β-HSD-2)、腎上腺細(xì)胞色素P450 1A1(CYP1A1)及其芳烴受體(AhR)的mRNA表達(dá)。結(jié)果從孕8日開始皮下注射尼古丁明顯導(dǎo)致大鼠IUGR的發(fā)生(P0.01)。尼古丁使孕鼠血清皮質(zhì)酮水平在孕中期及孕晚期均明顯升高(P0.05)。相對于對照組,孕中期及孕晚期尼古丁組孕鼠腎上腺St AR和P450scc的mRNA表達(dá)水平顯著升高(P0.05,P0.01),但是胎鼠腎上腺的St AR和P450scc的mRNA表達(dá)水平則有下降趨勢(P=0.16,P=0.11)。同時,尼古丁組足月大鼠胎盤迷路區(qū)的病理形態(tài)學(xué)發(fā)生了明顯的改變,包括迷路區(qū)出血和滋養(yǎng)層細(xì)胞變性;并使孕中、晚期反映胎盤功能的孕鼠血清胎盤催乳素水平(P0.05)、血清雌三醇水平以及胎盤11β-HSD-2的mRNA表達(dá)顯著下降(P0.05)。尼古丁對母鼠腎上腺的CYP1A1和AhR的mRNA表達(dá)有一定的誘導(dǎo)作用,但是對胎鼠腎上腺的CYP1A1和AhR的mRNA表達(dá)沒有明顯影響。結(jié)論孕期接觸尼古丁可明顯導(dǎo)致IUGR的發(fā)生,且與母體及胎兒甾體激素內(nèi)環(huán)境紊亂密切相關(guān)。
[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.
【作者單位】: 中國人民武裝警察部隊廣東省總隊醫(yī)院婦科;廣東省婦幼保健院產(chǎn)科;中國人民武裝警察部隊廣東省總隊醫(yī)院醫(yī)務(wù)處;
【基金】:廣東省中醫(yī)藥局建設(shè)中醫(yī)藥強省科研課題(編號:20132091)
【分類號】:R714.5
【正文快照】: 511400)胎兒宮內(nèi)發(fā)育遲緩(intrauterine growth retarda-tion,IUGR)是指孕周大于37周,胎兒出生體質(zhì)量小于2 500 g,或胎兒體質(zhì)量低于其孕齡平均體質(zhì)量第10百分位數(shù),或低于其平均體質(zhì)量的2個標(biāo)準(zhǔn)差的病理性胎兒生長受限[1]。正常妊娠人群中IUGR發(fā)生率大約為5%[2]。IUGR患兒圍產(chǎn)
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