Endothelial superoxide production is altered in sheep programmed by early gestation dexamethasone exposure.
Endothelial superoxide production is altered in sheep programmed by early gestation dexamethasone exposure.
复制标题
妊娠早期接触地塞米松会改变绵羊内皮超氧化物的产生。
DOI：
10.1159/000105521
复制
发表时间：
2008
期刊：
影响因子：
2.5
通讯作者：
Segar,JeffreyL
中科院分区：
文献类型：
--
作者：
Roghair,RobertD;MillerJr,FrancisJ;Scholz,ThomasD;Lamb,FredS;Segar,JeffreyL
背景：动物模型已经证明，母亲营养不良或妊娠早期糖皮质激素暴露诱导内皮功能障碍的production.Objectives：我们试图确定是否妊娠早期地塞米松（DEX）暴露进一步与血管超氧阴离子production.Methods：DEX（0.28 mg/kg/天静脉注射48小时）在妊娠27-28天（任期145天）的怀孕母羊。从DEX暴露组和对照组的羔羊在妊娠125天（每组n = 6）和分娩后4个月（分别n = 9和12）收获组织。结果：通过光泽精增强的化学发光，DEX暴露组胎儿的冠状动脉和肠系膜动脉表现出基础超氧化物产生减少（均p < 0.01）。同样地，通过内皮细胞培养和二氢乙锭荧光，来自4月龄羔羊的DEX暴露的颈动脉减少了定位于内皮的超氧化物产生（p < 0.01）。相比之下，来自4个月大绵羊的暴露于DEX的冠状动脉增加了超氧化物的产生（p < 0.05）。尽管妊娠早期DEX暴露并不改变脂质过氧化，但DEX暴露与肾脏和大脑皮质顺乌头酸酶活性显著增加相关（与蛋白质氧化降低一致）。这些变化发生在没有改变肾皮质超氧化物歧化酶activity.Conclusions：我们的结论是，在DEX暴露模型的胎儿编程，内皮超氧化物生成和蛋白质氧化减少肠系膜和颈动脉循环。这与出生后冠状动脉特异性超氧化物产生增加形成对比。
Background:Animal models have demonstrated that maternal undernutrition or early gestation glucocorticoid exposure induces endothelial dysfunction in the offspring.Objectives:We sought to determine whether early gestation dexamethasone (DEX) exposure is further associated with increased vascular superoxide anion production.Methods:DEX (0.28 mg/kg/day i.v. for 48 h) was administered to pregnant ewes at 27–28 days’ gestation (term 145 days). Tissues were harvested from DEX-exposed and control lambs at 125 days’ gestation (n = 6 for each group) and 4 months following delivery (n = 9 and 12, respectively).Results:By lucigenin-enhanced chemiluminescence, coronary and mesenteric arteries from DEX-exposed fetuses exhibited diminished basal superoxide production (both p < 0.01). Similarly, DEX-exposed carotid arteries from 4-month-old lambs had decreased superoxide production (p < 0.01) that localized to the endothelium by endothelial cell culture and dihydroethidium fluorescence. In contrast, DEX-exposed coronary arteries from the 4-month-old sheep had increased superoxide production (p < 0.05). Although early gestation DEX exposure did not alter lipid peroxidation, DEX exposure was associated with significantly increased renal and cerebral cortex aconitase activity (consistent with decreased protein oxidation). These changes occurred in the absence of alterations in renal cortex superoxide dismutase activity.Conclusions:We conclude that in a DEX-exposure model of fetal programming, endothelial superoxide production and protein oxidation are decreased in the mesenteric and carotid circulation. This contrasts with the postnatal coronary artery-specific increase in superoxide production.