目的研究褪黑素(MT)对细菌脂多糖(LPS)引起宫内胎儿死亡(IUFD)和生长发育迟缓(IUGR)的保护作用。方法实验1:LPS组小鼠于受孕第15-17天每天经腹腔注射LPS(75μg/kg),LPS+MT组在LPS处理前和(或)处理后经腹腔注射MT,生理盐水和单纯MT处理作为对照。所有孕鼠于受孕第18天处死,统计活胎、死胎和吸收胎数,称量活胎体重,测量胎鼠身长和尾长,并对胎鼠骨骼发育情况进行评价。实验2:LPS组小鼠于受孕第16天经腹腔一次性注射75μg/kg LPS,LPS+MT组孕鼠于LPS处理前和(或)处理后经腹腔注射MT,生理盐水和单纯MT处理作为对照。LPS处理后6h处死孕鼠,取母肝和胎盘,检测丙二醛和谷胱甘肽水平。结果LPS+MT处理组宫内胎儿死亡数显著低于单纯LPS处理组,并呈明显剂量-效应关系;MT预+后和后处理均显著减轻LPS引起生长发育迟缓,并逆转LPS引起的枕骨骨化不全。MT预+后处理明显减轻LPS引起的母肝和胎盘脂质过氧化,但对LPS所致GSH含量降低无明显影响。结论MT通过其抗氧化功能保护LPS引起的IUFD和IUGR。
Objective To investiagate the effects of melatonin on LPS-induced intra-uterine fetal death (IUFD) and intra-uterine growth retardation (IUGR) in mice. Methods The present study included two separate experiments. Experiment 1, All pregnant mice except controls received an intraperitoneal injection of LPS (75 μg/kg, ip) on gd 15 - 17. The experiment was carried out in two different modes. In mode A, the pregnant mice received two doses of melatonin in 24 h, one ( 10 mg/kg, ip) injected immediately after LPS and the other ( 10 mg/kg, ip) injected at 3 h after LPS. In mode B, the pregnant mice were pretreated with 10 mg/kg of melatonin at 18 h before LPS and then received two doses of melatonin in 24 h, one ( 10 mg/kg, ip) injected immediately after LPS and the other ( 10 mg/kg, ip) injected at 3 h after LPS. The number of live fetuses, dead fetuses and resorption sites were counted on gd 18. Live fetuses in each litter were weighed. Crown-rump and tail lengths were examined and skeletal development was evaluated. Experiment 2, All pregnant mice except controls ( either saline or melatonin) received an intraperitoneal (75μg/kg) injection of LPS on gd 16. In mode A, the pregnant mice received two doses of melatonin, one ( 10 mg/kg, ip) injected immediately after LPS and the other ( 10 mg/kg, ip) injected at 3 h after LPS; In mode B, the pregnant mice were pretreated with 10 mg/kg of melatonin at 18 h before LPS and then received two doses of melatonin, one ( 10 mg/kg, ip) injected immediately after LPS and the other ( 10 mg/kg, ip) injected at 3 h after LPS. All dams were sacrificed at 6 h after LPS treatment. Maternal liver and placenta were dissected for GSH and MDA measurements. Results Post-treatment with melatonin significantly attenuated LPS-induced IUFD. Surprisingly, pre- plus post-treatments with melatonin almost blocked LPS-induced IUFD. In addition, both post-treatment and pre- plus post-treatments with melatonin significantly alleviated LPS-induced dec