Nash Peppi, Olovsson Matts, Eriksson Ulf J
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
J Soc Gynecol Investig. 2005 Apr;12(3):174-84. doi: 10.1016/j.jsgi.2004.12.002.
The aim of the present study was to evaluate a rat model of placental dysfunction/preeclampsia in pregnancies complicated by maternal diabetes. A second objective was to evaluate the effects of vitamin E treatment in this model.
Normal and streptozotocin-induced diabetic rats of two different strains (U and H) were given intraperitoneal (IP) injections of the angiogenesis inhibitor Suramin (Sigma Chemical Co, St Louis, MO) or saline in early pregnancy, and fed standard or vitamin E-enriched food. The outcome of pregnancy was evaluated on gestational day 20.
In both rat strains Suramin caused fetal growth retardation, decreased placental blood flow, and increased placental concentration of the isoprostane 8-iso-PGF(2alpha). In the U rats Suramin also caused increased fetal resorption rate, increased maternal blood pressure, decreased renal blood flow, and diminished maternal growth. Diabetes caused severe maternal and fetal growth retardation, increased resorption rate, and increased placental 8-iso-PGF(2alpha) concentration independent of Suramin administration. The maternal and fetal effects of Suramin and diabetes were more pronounced in the U strain than in the H strain. Vitamin E treatment improved the status of Suramin-injected diabetic rats: in U rats the blood pressure increase was normalized; and in both U and H rats the decreased placental blood flow was marginally enhanced, and the increase in placental 8-iso-PGF(2alpha) was partly normalized by vitamin E.
Suramin injections to pregnant rats cause a state of placental insufficiency, which in U rats resembles human preeclampsia. The induction of this condition is at least partly mediated by oxidative stress, and antagonized by antioxidative treatment. Maternal diabetes involves increased oxidative stress, and causes both maternal and fetal morbidity, which are only marginally affected by additional Suramin treatment.
本研究旨在评估妊娠合并母体糖尿病时胎盘功能障碍/子痫前期的大鼠模型。第二个目的是评估维生素E治疗在此模型中的效果。
对两种不同品系（U和H）的正常及链脲佐菌素诱导的糖尿病大鼠在妊娠早期腹腔注射血管生成抑制剂苏拉明（Sigma化学公司，密苏里州圣路易斯）或生理盐水，并给予标准饲料或富含维生素E的饲料。在妊娠第20天评估妊娠结局。
在两种品系的大鼠中，苏拉明均导致胎儿生长受限、胎盘血流减少以及胎盘异前列腺素8-异-PGF(2α)浓度升高。在U品系大鼠中，苏拉明还导致胎儿吸收率增加、母体血压升高、肾血流减少以及母体生长减缓。糖尿病导致严重的母体和胎儿生长受限、吸收率增加以及胎盘8-异-PGF(2α)浓度升高，且与苏拉明给药无关。苏拉明和糖尿病对母体和胎儿的影响在U品系中比在H品系中更明显。维生素E治疗改善了注射苏拉明的糖尿病大鼠的状况：在U品系大鼠中血压升高恢复正常；在U品系和H品系大鼠中，胎盘血流减少均略有改善，胎盘8-异-PGF(2α)的升高部分被维生素E恢复正常。
给妊娠大鼠注射苏拉明会导致胎盘功能不全状态，在U品系大鼠中类似于人类子痫前期。这种情况的诱导至少部分由氧化应激介导，并可被抗氧化治疗拮抗。母体糖尿病涉及氧化应激增加，并导致母体和胎儿发病，额外的苏拉明治疗对其影响很小。
Zotero 插件