Wang Y, Walsh S W
Department of Obstetrics and Gynecology, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA.
Free Radic Biol Med. 1995 Mar;18(3):585-91. doi: 10.1016/0891-5849(94)00157-f.
Preeclampsia is a hypertensive disorder of human pregnancy that is a leading cause of premature delivery and fetal growth retardation. It is characterized by hypertension, reduced uteroplacental blood flow, proteinuria, and edema. Preeclampsia is associated with an imbalance of increased thromboxane and decreased prostacyclin, as well as with an imbalance of increased lipid peroxides and decreased antioxidants. Low-dose aspirin (ASA) therapy (60-150 mg/day) is being evaluated for the prevention of preeclampsia. The rationale for this is that low-dose ASA selectively inhibits thromboxane synthesis without affecting prostacyclin synthesis. We hypothesized that ASA might also inhibit the synthesis of lipid peroxides. The purpose of this study was to examine the effects of aspirin on lipid peroxide, thromboxane, and prostacyclin production rates in placentas obtained from women with preeclampsia. Placentas were obtained from five preeclamptic women. Placental tissues (350 mg) were incubated in Dulbecco's Modified Eagles Medium (DMEM) for 48 h, alone and with varying concentrations of aspirin: 1 x 10(-6) M, 1 x 10(-5) M, 5 x 10(-5) M, 1 x 10(-4) M, and 5 x 10(-4) M. Samples were collected at 0, 2, 6, 16, 28, and 48 h of incubation, and analyzed for thromboxane and prostacyclin by RIA of their stable metabolites, thromboxane B2 and 6-keto-PGF1 alpha, and for lipid peroxides by peroxide equivalents. As compared to control, an aspirin concentration of 5 x 10(-5) M significantly inhibited (p < 0.05) both lipid peroxides (3.15 +/- 0.49 vs. 1.90 +/- 0.31 pmol/microgram/h) and thromboxane (0.66 +/- 0.11 vs. 0.32 +/- 0.10 pg/microgram/h), but not prostacyclin (0.24 +/- 0.05 vs. 0.17 +/- 0.02 pg/microgram/h, p > 0.05). Lower aspirin doses (1 x 10(-6) M, 1 x 10(-5) M) had no effect, whereas higher doses (1 x 10(-4) M and 5 x 10(-4) M) inhibited all three compounds. We conclude that aspirin inhibits lipid peroxides, as well as thromboxane and prostacyclin, in preeclamptic placentas. The inhibitory effects are dose dependent. Low-dose aspirin (5 x 10(-5) M) selectively inhibits lipid peroxides and thromboxane without affecting prostacyclin. We speculate that the selective inhibitory effect of low-dose aspirin may account for its effectiveness in the prevention of preeclampsia.
子痫前期是一种人类妊娠期高血压疾病，是早产和胎儿生长受限的主要原因。其特征为高血压、子宫胎盘血流减少、蛋白尿和水肿。子痫前期与血栓素增加和前列环素减少的失衡有关，也与脂质过氧化物增加和抗氧化剂减少的失衡有关。低剂量阿司匹林（ASA）疗法（60 - 150毫克/天）正在被评估用于预防子痫前期。其理论依据是低剂量ASA能选择性抑制血栓素合成而不影响前列环素合成。我们推测ASA可能也抑制脂质过氧化物的合成。本研究的目的是检测阿司匹林对取自子痫前期患者的胎盘脂质过氧化物、血栓素和前列环素生成率的影响。从五名单纯子痫前期患者获取胎盘。将胎盘组织（350毫克）在杜氏改良伊格尔培养基（DMEM）中单独孵育以及与不同浓度的阿司匹林（1×10⁻⁶摩尔/升、1×10⁻⁵摩尔/升、5×10⁻⁵摩尔/升、1×10⁻⁴摩尔/升和5×10⁻⁴摩尔/升）一起孵育48小时。在孵育0、2、6、16、28和48小时时收集样本，通过放射免疫分析法（RIA）检测其稳定代谢产物血栓素B2和6 - 酮 - PGF1α来分析血栓素和前列环素，并通过过氧化物当量分析脂质过氧化物。与对照组相比，5×10⁻⁵摩尔/升的阿司匹林浓度显著抑制（p < 0.05）脂质过氧化物（3.15 ± 0.49对1.90 ± 0.31皮摩尔/微克/小时）和血栓素（0.66 ± 0.11对0.32 ± 0.10皮克/微克/小时），但不抑制前列环素（0.24 ± 0.05对0.17 ± 0.02皮克/微克/小时，p > 0.05）。较低剂量的阿司匹林（1×10⁻⁶摩尔/升、1×10⁻⁵摩尔/升）无作用，而较高剂量（1×10⁻⁴摩尔/升和5×10⁻⁴摩尔/升）抑制所有三种化合物。我们得出结论，阿司匹林抑制子痫前期胎盘的脂质过氧化物、血栓素和前列环素。抑制作用呈剂量依赖性。低剂量阿司匹林（5×10⁻⁵摩尔/升）选择性抑制脂质过氧化物和血栓素而不影响前列环素。我们推测低剂量阿司匹林的选择性抑制作用可能解释了其预防子痫前期的有效性。
