Department of Obstetrics, Preterm Birth Prevention and Treatment Research Unit, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Department of Blood Transfusion, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Biosci Rep. 2019 Jul 2;39(7). doi: 10.1042/BSR20190386. Print 2019 Jul 31.
Our previous work has shown that nicotine suppressed lipopolysaccharide (LPS)-induced placental inflammation by inhibiting cytokine release as well as infiltration of leukocytes into the placenta through the cholinergic anti-inflammatory pathway. Nicotine also increased fetal survival and restored pup weight. In the present study, we aim to further investigate if fetal growth restriction (FGR) occurs with LPS treatment, and evaluate the protective effects of nicotine on fetuses in late gestation of rats. Pregnant Sprague-Dawley rats were divided into control group, nicotine group, LPS group and LPS + nicotine group. Rats were first pretreated with nicotine or vehicle by subcutaneous injection on gestation day (GD)14 and GD15, followed by LPS or vehicle intraperitoneal injection on GD16, and were killed on GD18. Loss of fetuses, number and weights of live fetuses and weights of placentas were recorded. Placentas were collected to evaluate placental pathology and determine inflammatory cytokines and vascular endothelial growth factor (VEGF) levels. We found that LPS treatment increased levels of placental inflammatory cytokines and placental pathological damage, decreased levels of VEGF, reduced number of live fetuses and induced FGR. Pretreatment with nicotine reversed LPS-induced high levels of placental inflammatory cytokines, low levels of placental VEGF and placental pathological damage, then rescued the number and weights of live fetuses. These data demonstrated that activation of the cholinergic anti-inflammatory pathway by nicotine protected fetus against LPS-induced FGR through ameliorating placental inflammation and vascular development in late pregnancy in rats. It may be an alternative therapeutic strategy for inflammation- induced FGR in late pregnancy.
我们之前的研究表明，尼古丁通过胆碱能抗炎途径抑制细胞因子释放和白细胞浸润到胎盘，从而抑制脂多糖（LPS）诱导的胎盘炎症。尼古丁还增加了胎儿的存活率并恢复了幼崽的体重。在本研究中，我们旨在进一步研究 LPS 处理是否会导致胎儿生长受限（FGR），并评估尼古丁对孕晚期大鼠胎儿的保护作用。将妊娠 Sprague-Dawley 大鼠分为对照组、尼古丁组、LPS 组和 LPS+尼古丁组。大鼠首先在妊娠第 14 天和第 15 天通过皮下注射接受尼古丁或载体预处理，然后在第 16 天进行 LPS 或载体腹腔注射，并在第 18 天处死。记录胎儿丢失、活胎数量和体重以及胎盘重量。收集胎盘评估胎盘病理并测定炎症细胞因子和血管内皮生长因子（VEGF）水平。我们发现，LPS 处理增加了胎盘炎症细胞因子水平和胎盘病理损伤，降低了 VEGF 水平，减少了活胎数量并导致 FGR。尼古丁预处理逆转了 LPS 诱导的胎盘炎症细胞因子升高、胎盘 VEGF 水平降低和胎盘病理损伤，从而挽救了活胎的数量和体重。这些数据表明，尼古丁激活胆碱能抗炎途径通过改善孕晚期大鼠胎盘炎症和血管发育来保护胎儿免受 LPS 诱导的 FGR。它可能是治疗孕晚期炎症诱导的 FGR 的一种替代治疗策略。
