Carbon monoxide inhibits hypoxia/reoxygenation-induced apoptosis and secondary necrosis in syncytiotrophoblast
Carbon monoxide inhibits hypoxia/reoxygenation-induced apoptosis and secondary necrosis in syncytiotrophoblast
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DOI：
10.2353/ajpath.2006.060184
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发表时间：
2006-09-01
影响因子：
6
通讯作者：
Smith, Graeme N.
中科院分区：
文献类型：
--
作者：
Bainbridge, Shannon A.;Belkacemi, Louiza;Smith, Graeme N.
先兆子痫是一种妊娠期高血压疾病，影响5%至7%的妊娠。氧化应激诱导的胎盘损伤和随后胎盘碎片释放到母体循环中是先兆子痫进展中的关键致病事件。在整个怀孕期间吸烟的妇女比不吸烟的妇女患这种疾病的可能性低33%。我们推测吸烟妇女血清中一氧化碳浓度升高可抑制缺血再灌注损伤时滋养层细胞的凋亡和碎片脱落，因为一氧化碳对培养的内皮细胞和平滑肌细胞具有细胞保护作用。这可能是负责降低吸烟妇女先兆子痫的风险。为了评估胎盘组织内一氧化碳的细胞保护特性，将一氧化碳处理施用于从足月人胎盘培养的体外缺氧/再氧损伤的绒毛外植体。使用分子和形态学方法评估细胞凋亡的诱导。胎盘绒毛外植体;与经历类似损伤的未处理外植体相比，用一氧化碳处理的分化的合体滋养层中缺氧/再氧诱导的细胞凋亡减少60%。此外，在一氧化碳处理的外植体中观察到完整的合胞膜保留。这些观察结果表明，一氧化碳在人胎盘中具有有效的抗凋亡特性，并可能在治疗先兆子痫中具有治疗潜力。
Pre-eclampsia, a hypertensive disorder of pregnancy, affects 5 to 7% of pregnancies. Oxidative stress-induced placental injury and subsequent release of placental debris into the maternal circulation are key pathogenic events in the progression of pre-eclampsia. Women who smoke cigarettes throughout pregnancy are 33% less likely to develop this disorder than nonsmoking women. We postulated that elevated carbon monoxide concentrations in serum of smoking women inhibits apoptosis and debris shedding of trophoblast cells exposed to ischemia-reperfusion injury because carbon monoxide has cytoprotective effects on endothelial and smooth muscle cells in culture. This may be responsible for the reduced risk of preeclampsia in smoking women. To assess the cytoprotective properties of carbon monoxide within placental tissue, carbon monoxide treatments were administered to in vitro hypoxia/reoxygenation-insulted villous explants cultured from term human placenta. Induction of apoptosis was assessed using molecular and morphological approaches. Placental villous explants; treated with carbon monoxide demonstrated 60% less hypoxia/reoxygenation-induced apoptosis in the differentiated syncytiotrophoblast layer compared with untreated explants undergoing a similar insult. In addition, retention of intact syncytial membranes was observed in carbon monoxide-treated explants. These observations indicate that carbon monoxide has potent antiapoptotic properties within human placenta and may hold therapeutic potential in the treatment of pre-eclampsia.