Refuerzo Jerrie S, Sokol Robert J, Aranda Jacob V, Hallak Mordechai, Hotra John W, Kruger Michael, Sorokin Yoram
Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Wayne State University, Detroit, MI 48201, USA.
Fetal Diagn Ther. 2006;21(3):259-63. doi: 10.1159/000091352.
To determine the effects of sildenafil citrate on fetal growth in maternal rats exposed to hypoxia.
Timed pregnant rats were randomized to either hypoxia or control on gestational days (GD) 18-20, and received either sildenafil (45 mg/kg) orally every 12 h on GD 18-21 or an equal volume of sterile water. Fetal pups were retrieved by laparotomy on GD 21. Pup weight and length were evaluated and cGMP measured in maternal and fetal blood.
In the non-hypoxic rats, sildenafil exposure was associated with a decrease in size(4.75 +/- 0.43 vs. 5.11 +/- 0.34 g, p = 0.00). In contrast, in the hypoxic rat model, sildenafil exposure was associated with increased size of the offspring (5.48 +/- 0.45 vs. 5.16 +/- 0.36 g, p = 0.016). Maternal cGMP levels were increased in the presence of both sildenafil and hypoxia (23.0 +/- 10.5 vs. 15.6 +/- 2.7 pmol/ml, p = 0.001).
Exposure to sildenafil in a non-hypoxic setting results in a decrease in fetal size. Sildenafil in the presence of a stimulus, hypoxia, will lead to increased fetal size. These results suggest that sildenafil may have some influence on fetal growth. How these effects occur and by what mechanism remain to be determined.
确定枸橼酸西地那非对暴露于低氧环境的孕鼠胎儿生长的影响。
将定时受孕的大鼠在妊娠第18 - 20天随机分为低氧组或对照组，并在妊娠第18 - 21天每12小时口服一次西地那非（45毫克/千克）或等体积的无菌水。在妊娠第21天通过剖腹术取出胎鼠。评估幼鼠体重和体长，并测量母鼠和胎鼠血液中的环磷酸鸟苷（cGMP）。
在非低氧大鼠中，暴露于西地那非与幼鼠体型减小有关（4.75±0.43克对5.11±0.34克，p = 0.00）。相比之下，在低氧大鼠模型中，暴露于西地那非与后代体型增大有关（5.48±0.45克对5.16±0.36克，p = 0.016）。在同时存在西地那非和低氧的情况下，母鼠的cGMP水平升高（23.0±10.5对15.6±2.7皮摩尔/毫升，p = 0.001）。
在非低氧环境中暴露于西地那非会导致胎儿体型减小。在低氧刺激存在的情况下，西地那非会导致胎儿体型增大。这些结果表明西地那非可能对胎儿生长有一定影响。这些影响如何发生以及通过何种机制仍有待确定。
