Boksa P
Douglas Hospital Research Centre, Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
Pediatr Res. 1997 Jan;41(1):34-43. doi: 10.1203/00006450-199701000-00006.
Circulating glucocorticoids play a role during the immediate postnatal period in adapting the neonate to extrauterine life and are also thought to influence tissue development and function in the later postnatal period. In the present study we have used a rat model to test whether birth by cesarean section (C-section), either alone or with an added period of acute anoxia, affects the development profile of basal corticosterone secretion during the first 5 wk of life. Plasma levels of total corticosterone and of corticosteroid-binding globulin were measured at various times after birth in rats born vaginally, by C-section, or by C-section with 15 min of added anoxia. These measures allowed for calculation of levels of free, biologically active, corticosterone. Under all conditions, total corticosterone appeared to accurately reflect levels of free corticosterone. Plasma corticosterone levels measured immediately (< 5 min) after birth were similar in male rat pups born vaginally, by C-section, or by C-section with added anoxia, whereas female pups born by C-section showed a significant increase in free corticosterone at birth, in comparison with vaginally born females. Both male and female animals born by C-section showed a reduction in plasma corticosterone at 1 h (male: 31% of control, p < 0.01; female: 45% of control, p < 0.05) and at 7 d (male: 61% of control, p < 0.01; female: 55% of control, p < 0.05) after birth, in comparison with vaginally born controls. In animals born by C-section with added anoxia, significant reductions in plasma corticosterone were observed for males at 1 h (58% of control; p < 0.05) and for females at 7 d (62% of control; p < 0.05) after birth. At 14 d of age, corticosterone levels were higher in male rats born by C-section either with (227% of control; p < 0.05) or without (239% of control; p < 0.05) added anoxia, in comparison with vaginally born controls. Thus C-section birth produces an early rise in plasma corticosterone on d 14 away from the low values associated with the adrenal quiescent period in the first 1-2 wk in the rat. By 35 d of age, there were no differences in plasma corticosterone attributable to C-section birth and/or acute birth anoxia, in either male or female rats. It is concluded that, in a rat model, birth by C-section has significant effects on the profile of plasma corticosterone during the early weeks of development, a period though to be critical for effects of corticosteroids on developing tissues. Because the rat at birth is developmentally less mature than is the term human neonate, these findings may have implications for development of the premature human neonate.
循环糖皮质激素在新生儿出生后的即刻阶段发挥作用,帮助新生儿适应宫外生活,并且也被认为会在出生后的后期阶段影响组织发育和功能。在本研究中,我们使用大鼠模型来测试剖宫产(C -section)单独进行,或加上一段急性缺氧期,是否会影响出生后前 5 周基础皮质酮分泌的发育模式。在经阴道分娩、剖宫产或剖宫产加 15 分钟缺氧处理的大鼠出生后的不同时间,测量血浆中总皮质酮和皮质类固醇结合球蛋白的水平。这些测量结果可用于计算游离的、具有生物活性的皮质酮水平。在所有条件下,总皮质酮似乎都能准确反映游离皮质酮的水平。出生后立即(<5 分钟)测量的血浆皮质酮水平,经阴道分娩、剖宫产或剖宫产加缺氧处理的雄性幼鼠相似,而剖宫产出生的雌性幼鼠与经阴道分娩的雌性相比,出生时游离皮质酮显著增加。与经阴道分娩的对照动物相比,剖宫产出生的雄性和雌性动物在出生后 1 小时(雄性:对照组的 31%,p<0.01;雌性:对照组的 45%,p<0.05)和 7 天(雄性:对照组的 61%,p<0.01;雌性:对照组的 55%,p<0.05)时血浆皮质酮降低。在剖宫产加缺氧处理出生的动物中,出生后 1 小时雄性(对照组的 58%;p<0.05)和 7 天雌性(对照组的 62%;p<0.05)的血浆皮质酮显著降低。在 14 日龄时,与经阴道分娩的对照相比,剖宫产加(对照组的 227%;p<0.05)或不加(对照组的 239%;p<0.05)缺氧处理出生的雄性大鼠皮质酮水平更高。因此,剖宫产出生会使大鼠在出生后第 14 天血浆皮质酮早期升高,偏离大鼠出生后前 1 - 2 周与肾上腺静止期相关的低值。到 35 日龄时,无论雄性还是雌性大鼠,剖宫产出生和/或急性出生缺氧对血浆皮质酮均无差异。得出的结论是,在大鼠模型中,剖宫产出生对发育早期几周的血浆皮质酮模式有显著影响,这一时期被认为是皮质类固醇对发育中组织产生影响的关键时期。由于出生时大鼠在发育上比足月人类新生儿不成熟,这些发现可能对早产人类新生儿的发育有影响。