Chronic hypoxia decreases endothelial nitric oxide synthase protein expression in fetal guinea pig hearts.
Chronic hypoxia decreases endothelial nitric oxide synthase protein expression in fetal guinea pig hearts.
复制标题
慢性缺氧会降低豚鼠胎儿心脏内皮一氧化氮合酶蛋白的表达。
DOI：
10.1016/j.jsgi.2005.04.011
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Dong,Yafeng
中科院分区：
文献类型：
--
作者：
Thompson,LorenP;Dong,Yafeng
目的：胎儿缺氧诱导适应的细胞机制尚不清楚。我们测试的假设，缺氧上调内皮型一氧化氮合酶（NOS 3，III型）的蛋白质表达在胎儿心脏中观察到的成人心脏作为一种心脏保护性适应相似。本研究探讨慢性缺氧对暴露于常氧或宫内hypoxia.Methods胎儿豚鼠的心脏和颈动脉中NOS 3蛋白表达的影响：时间交配怀孕豚鼠（任期= 65天）被安置在常氧室内空气（NMX）或暴露于12%O2（缺氧; HPX）的持续时间为14或28天。在近足月（妊娠约60天）时，麻醉妊娠母体，从NMX和HPX动物中切除胎豚鼠心脏和颈动脉，并冷冻直至研究准备就绪。此外，还从暴露于NMX或HPX 14天的麻醉成年非妊娠雌性豚鼠中切除心脏。从所有组织中提取NOS 3蛋白，并使用Western印迹分析进行定量。胎儿心脏样本也准备了NOS 3蛋白的定位using immunohistochemistry.Results：慢性缺氧增加产妇和胎儿红细胞压积后28天的时间。与NMX对照组相比，HPX在28天后使胎豚鼠心脏中的NOS 3蛋白水平降低了29%。相比之下，HPX暴露14天后，与相应的NMX对照组相比，成人心脏中的NOS 3孕酮水平增加了62%，胎儿颈动脉中的NOS 3孕酮水平增加了4倍。NOS 3蛋白的阳性免疫染色定位于心肌细胞和内皮细胞。结论：与我们的假设相反，缺氧诱导的胎儿豚鼠心脏NOS 3蛋白的下降与成人心脏或胎儿颈动脉中的蛋白水平测量相反。这些结果表明，NOS蛋白的表达改变不同的缺氧在胎儿和成人的心脏和周围胎儿动脉暴露于相同水平的缺氧。因此，NO在胎儿心脏缺氧过程中的功能作用可能与成人不同。
Objectives:The underlying cellular mechanisms mediating hypoxia-induced adaptations in the fetus are poorly understood. We tested the hypothesis that hypoxia up-regulates endothelial nitric oxide synthase (NOS3, type III) protein expression in fetal hearts similar to that observed in adult hearts as a cardioprotective adaptation. This study investigates the effect of chronic hypoxia on NOS3 protein expression in hearts and carotid arteries of fetal guinea pigs exposed to normoxia or intrauterine hypoxia.Methods:Time-mated pregnant guinea pigs (term = 65 days) were housed in either normoxic room air (NMX) or exposed to 12% O2(hypoxia; HPX) for 14 or 28 days of duration. At near term (∼60 days of gestation), pregnant mothers were anesthetized and fetal guinea pig hearts and carotid arteries were excised from NMX and HPX animals and frozen until ready for study. In addition, hearts were also excised from anesthetized adult nonpregnant female guinea pigs exposed to either NMX or HPX for 14 days. NOS3 protein was extracted from all tissues and quantified using Western blot analysis. Fetal heart samples were also prepared for localization of NOS3 protein using immunohistochemistry.Results:Chronic hypoxia increased both maternal and fetal hematocrit after 28 days of duration. HPX decreased NOS3 protein levels in fetal guinea pig hearts by 29% after 28 days compared to NMX controls. In contrast, HPX increased both NOS3 progein levels in adult hearts by 62% and fetal carotid arteries by fourfold after 14 days of exposure compared to their respective NMX controls. Positive immunostaining of NOS3 protein of fetal hearts was localized in both cardiomyocytes and endothelial cells.Conclusion:Contrary to our hypothesis, the hypoxia-induced decrease in fetal guinea pig heart NOS3 protein contrasts to the protein levels measured in either adult hearts or fetal carotid arteries. These results suggest that the NOS protein expression is altered differently by hypoxia in fetal and adult hearts and in a peripheral fetal artery exposed to the same level of hypoxia. Thus, the functional role of NO in the fetal heart during hypoxia may differ from that of the adult.