A New Oxidative Stress Model, 2,2-Azobis(2-Amidinopropane) Dihydrochloride Induces Cardiovascular Damages in Chicken Embryo
A New Oxidative Stress Model, 2,2-Azobis(2-Amidinopropane) Dihydrochloride Induces Cardiovascular Damages in Chicken Embryo
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一种新的氧化应激模型，2,2-偶氮双(2-脒基丙烷)二盐酸盐诱导鸡胚胎心血管损伤
DOI：
10.1371/journal.pone.0057732
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发表时间：
2013-03-01
期刊：
影响因子：
3.7
通讯作者：
Kurihara, Hiroshi
中科院分区：
文献类型：
--
作者：
He, Rong-Rong;Li, Yan;Kurihara, Hiroshi
现在已经确定，发育中的胚胎对氧化应激非常敏感，这是导致妊娠相关疾病的一个因素。然而，由于在胎盘中缺乏适当的ROS控制方法，对活性氧（ROS）对胚胎心血管系统的影响知之甚少。本研究利用自由基产生物- 2,2-偶氮（2-氨基丙烷）二盐酸（AAPH）小分子，研究了氧化应激对鸡胚发育过程中心血管系统的影响。用不同浓度的AAPH在气室中处理9日龄（HH 35期）鸡胚，确定AAPH的LD50值为10µmol/蛋。在此浓度下，AAPH可显著降低HH - 35鸡胚绒毛尿囊膜（CAM）血管丛的密度。研究了AAPH对幼龄胚的影响，发现AAPH能抑制HH - 18胚卵黄囊血管丛的发育。AAPH还显著抑制HH 3+胚胎的血岛发育。这些结果表明，aaph诱导的氧化应激可损害与血管生成和血管生成相关的整个发育过程。此外，我们在AAPH治疗后的HH 40胚胎中观察到心脏增大，其中左心室和室间隔由于心肌细胞肥大而呈剂量依赖性增厚。由此可见，AAPH诱导的氧化应激可导致发育中的鸡胚心血管系统的损伤。本研究还提供了一种新的发育模型，作为动物和细胞模型的替代，用于测试具有抗氧化活性的小分子和药物。
It is now well established that the developing embryo is very sensitive to oxidative stress, which is a contributing factor to pregnancy-related disorders. However, little is known about the effects of reactive oxygen species (ROS) on the embryonic cardiovascular system due to a lack of appropriate ROS control method in the placenta. In this study, a small molecule called 2,2-azobis(2-amidinopropane) dihydrochloride (AAPH), a free radicals generator, was used to study the effects of oxidative stress on the cardiovascular system during chick embryo development. When nine-day-old (stage HH 35) chick embryos were treated with different concentrations of AAPH inside the air chamber, it was established that the LD50 value for AAPH was 10 µmol/egg. At this concentration, AAPH was found to significantly reduce the density of blood vessel plexus that was developed in the chorioallantoic membrane (CAM) of HH 35 chick embryos. Impacts of AAPH on younger embryos were also examined and discovered that it inhibited the development of vascular plexus on yolk sac in HH 18 embryos. AAPH also dramatically repressed the development of blood islands in HH 3+ embryos. These results implied that AAPH-induced oxidative stress could impair the whole developmental processes associated with vasculogenesis and angiogenesis. Furthermore, we observed heart enlargement in the HH 40 embryo following AAPH treatment, where the left ventricle and interventricular septum were found to be thickened in a dose-dependent manner due to myocardiac cell hypertrophy. In conclusion, oxidative stress, induced by AAPH, could lead to damage of the cardiovascular system in the developing chick embryo. The current study also provided a new developmental model, as an alternative for animal and cell models, for testing small molecules and drugs that have anti-oxidative activities.