Edwards A D, Yue X, Cox P, Hope P L, Azzopardi D V, Squier M V, Mehmet H
Department of Paediatrics and Neonatal Medicine, Royal Postgraduate Medical School, London.
Pediatr Res. 1997 Nov;42(5):684-9. doi: 10.1203/00006450-199711000-00022.
This study addressed the hypothesis that in human infants severe in utero insults induce a significant proportion of brain cells to undergo apoptosis. Morphologic criteria were used to quantify apoptosis and necrosis in the cingulate gyrus of two groups of infants: six infants who died after severe birth asphyxia with hypoxic-ischemic encephalopathy, and six others who suffered unexpected and apparently sudden intrauterine death at or close to term. The fraction of apoptotic cells was much higher than basal levels determined in animal experiments, and within both groups increased in proportion to the severity of injury as determined by total cell death (p < 0.05). The mean fraction of apoptotic cells was similar in asphyxiated infants, 8.3% (95% confidence interval for the population, 3.7-12%), and in stillbirths, 6.7% (0.2-13.6%). In the asphyxiated group, 20.8% (11-30.6%) of cells were necrotic, but significantly less necrosis, 3% (0.4-5.6%), was seen in stillborn infants (p < 0.05). Cell death was apoptotic after birth asphyxia in 26% (1-51%) and 78% (41-100%) in stillborn infants. In situ end labeling studies confirmed the presence of DNA fragmentation in apoptotic cells. These results demonstrate that infants who die after intrauterine insults, both those with evidence of delayed cerebral injury after hypoxia-ischemia and those without, have a significant number of cells in the brain with the morphologic characteristics of apoptosis. They confirm that apoptosis contributes significantly to cerebral damage in the perinatal period.
在人类婴儿中，子宫内严重损伤会导致相当比例的脑细胞发生凋亡。采用形态学标准对两组婴儿扣带回中的凋亡和坏死情况进行量化：一组是6名出生时严重窒息并伴有缺氧缺血性脑病后死亡的婴儿，另一组是6名在足月或接近足月时意外且明显突然发生宫内死亡的婴儿。凋亡细胞的比例远高于动物实验中确定的基础水平，并且在两组中，凋亡细胞比例均随全细胞死亡所确定的损伤严重程度增加而升高（p<0.05）。窒息婴儿的凋亡细胞平均比例为8.3%（总体95%置信区间为3.7 - 12%），死产婴儿的凋亡细胞平均比例为6.7%（0.2 - 13.6%），二者相似。在窒息组中，20.8%（11 - 30.6%）的细胞发生坏死，但死产婴儿中坏死细胞比例显著更低，为3%（0.4 - 5.6%）（p<0.05）。出生窒息后细胞死亡为凋亡性的比例在死产婴儿中为26%（1 - 51%），在窒息婴儿中为78%（41 - 100%）。原位末端标记研究证实凋亡细胞中存在DNA片段化。这些结果表明，子宫内损伤后死亡的婴儿，无论是有缺氧缺血后迟发性脑损伤证据的，还是没有该证据的，其大脑中都有大量具有凋亡形态学特征的细胞。这些结果证实凋亡在围生期脑损伤中起重要作用。
