Department of Physiology and Physiological Chemistry, University of Kwa Zulu-Natal, Durban, South Africa.
Eur J Obstet Gynecol Reprod Biol. 2011 Aug;157(2):136-40. doi: 10.1016/j.ejogrb.2011.03.005. Epub 2011 Apr 9.
We have previously shown that sildenafil citrate improves various fetal outcomes in pregnant, L-NAME treated, Sprague-Dawley rats. We therefore aimed to identify which component/s of this diverse pathophysiologic cascade is/are improved by this drug.
This study is a sub-analysis of plasma samples obtained in a previous study in which 24 pregnant Sprague-Dawley dams were divided into three groups (n=8) i.e. the control group (CON), the experimental control group (PRE) where the pre-eclampsia-like symptoms were induced using l-NAME, and the experimental group (SCT) where the pre-eclampsia-like symptoms were once again induced using L-NAME but these animals were treated with sildenafil citrate. On gestation day 20 blood samples were collected in heparin-coated tubes and plasma samples were then analysed for specific variables using commercially available kits for rats.
There was a significant increase in the plasma levels of soluble fms-like tyrosine kinase1 (sFlt-1) in the PRE group (1228.80±116.29 pg/ml) when compared to the CON (774.91±26.81 pg/ml) and SCT (698.98±20.78 pg/ml) groups, respectively (p<0.001). The plasma levels of soluble endoglin (sEng) were significantly decreased in the SCT group (149.47±3.72 ng/ml) when compared to the CON (178.52±5.33 ng/ml) and PRE (183.44±8.294 ng/ml) groups, respectively (p<0.01). Plasma nitric oxide and l-arginine levels showed a decreasing trend in the PRE groups when compared to the control (CON) and treated (SCT) groups, respectively.
Sildenafil citrate reduces the plasma levels of anti-angiogenic factors, sFlt-1 and sEng, in pre-eclamptic (L-NAME induced) Sprague-Dawley rats and may therefore be responsible for the reduction in blood pressure and proteinuria as well as the improved fetal outcomes noted in an earlier study.
我们之前的研究表明，枸橼酸西地那非可改善 L-NAME 处理的妊娠 Sprague-Dawley 大鼠的多种胎儿结局。因此，我们旨在确定该药物改善了这种多样化病理生理级联反应的哪个组成部分。
本研究是对之前研究中获得的血浆样本的亚分析，其中 24 只妊娠 Sprague-Dawley 孕鼠分为三组（n=8），即对照组（CON）、实验对照组（PRE），其中使用 L-NAME 诱导子痫前期样症状，实验组（SCT），其中再次使用 L-NAME 诱导子痫前期样症状，但这些动物用枸橼酸西地那非治疗。在妊娠第 20 天，用肝素涂覆的管收集血液样本，然后使用商业上可用于大鼠的试剂盒分析血浆样本中的特定变量。
与 CON（774.91±26.81pg/ml）和 SCT（698.98±20.78pg/ml）组相比，PRE 组的血浆可溶性 fms 样酪氨酸激酶 1（sFlt-1）水平显著升高（1228.80±116.29pg/ml）（p<0.001）。与 CON（178.52±5.33ng/ml）和 PRE（183.44±8.294ng/ml）组相比，SCT 组的血浆可溶性内皮糖蛋白（sEng）水平显著降低（149.47±3.72ng/ml）（p<0.01）。与对照组（CON）和治疗组（SCT）相比，PRE 组的血浆一氧化氮和 l-精氨酸水平呈下降趋势。
枸橼酸西地那非可降低子痫前期（L-NAME 诱导）Sprague-Dawley 大鼠的抗血管生成因子 sFlt-1 和 sEng 血浆水平，因此可能是导致血压和蛋白尿降低以及早期研究中观察到的胎儿结局改善的原因。
