The redox environment surrounding lung epithelia is collapsed in the infants exposed antenatally to placental infection with subsequent bronchopulmonary dysplasia

虽然几乎没有临床证据表明肺损伤是否实际发生在绒毛膜炎胎儿中，但这可能意味着一些BPD婴儿在子宫内就已经遭受了实质性肺损伤。我们先前已经表明，在大多数中/重度BPD婴儿中，血浆KL-6水平在脐带血血浆中已经升高，特别是当婴儿暴露于绒毛膜炎时。因此，与绒毛膜炎相关的产前肺损伤似乎通常具有引发效应，使胎儿肺对随后的毒性药物更敏感，而不是宫内感染直接引起的肺损伤。近年来，人们逐渐认识到细胞/组织周围的氧化还原环境可能影响细胞的生存能力，如生长、分化或凋亡。我们假设，当婴儿暴露于胎盘感染时，肺上皮衬里液的氧化还原环境可能会崩溃，并可能导致严重BPD的发展，因为他们的肺的生长/分化受损。我们测量了在妊娠28周前出生的早产儿肺上皮衬里液中主要小分子抗氧化剂（如抗坏血酸、谷胱甘肽和尿酸）的氧化还原比。因此，在随后发生BPD的胎盘感染婴儿中，脱氢抗坏血酸/还原型抗坏血酸和谷胱甘肽二硫化物/还原型谷胱甘肽的比值均增加。尤其是脱氢抗坏血酸/还原抗坏血酸比值与脐血血浆IgM和KL-6的值有较好的相关性。因此，这清楚地表明，肺上皮衬里液的氧化还原环境失调的胎盘感染的婴儿。

Although there is little clinical evidence about whether or not lung injury practically occurs in fetuses with chorioamnionitis, this possibly means that some of the infants with BPD had already suffered parenchymal lung injury while in utero. We have previously shown that, in most of moderate/severe BPD infants, the plasma KL-6 level was already increased in the cord blood plasma, especially when the infants were exposed to chorioamnionitis. Therefore, it seems likely that prenatal lung injury associated with chorioamnionitis usually has a priming effect that predisposes fetal lungs to become more susceptible to subsequent toxic agents, rather than lung injury being directly induced by intrauterine infection. Recently, it is gradually known that the redox environment surrounding cells / tissues possibly influence the cellular viability such as growth, differentiation, or apoptosis. We hypothesized that the redox environment of pulmonary epithelial lining fluids may be collapsed when the infants were exposed to placental infections, and may lead to the development of severe BPD because of impaired growth / differentiation of their lungs. We measured the oxidized to reduced ratio of major small-molecular antioxidants in pulmonary epithelial lining fluids such as ascorbic acid, glutathione, and uric acid in the preterm infants born before 28 week gestation. As a result, both of the ratios of dehydroascorbic acid / reduced ascorbic acid and glutathione disulfide / reduced glutathione were increased in the infants with placental infections subsequently developed BPD. Especially, dehydroascorbic acid / reduced ascorbic acid ratio was in good correlation with the values of IgM and KL-6 in cord blood plasma. Therefore, it was clearly shown that the redox environment of pulmonary epithelial lining fluids was dysregulated in the infants with placental infection.