Betamethasone and the Rhesus Fetus: Effect on Lung Morphometry and Connective Tissue
Betamethasone and the Rhesus Fetus: Effect on Lung Morphometry and Connective Tissue
复制标题
倍他米松和恒河猴胎儿：对肺形态测量和结缔组织的影响
作者：
J. Beck;W. Mitzner;John W. C. Johnson;G. Hutchins;J. Foidart;W. London;A. Palmer;R. Scott
摘要：足月妊娠率为 67% 至 85% 的怀孕恒河猴（Macaca mulatta）接受倍他米松治疗 3 天，然后剖腹产。与胎龄匹配的对照组（22.9 × 3.2 ml/kg 体重；P < 0.025）相比，这些治疗的胎儿具有更大的肺体积（32.6 × 1.8 ml/kg 体重），但通过羊水 L/S 比率、肺泡通气稳定性或肺磷脂酰胆碱测量的表面活性剂性质没有变化。这些发现表明，倍他米松通过改变肺泡表面活性剂浓度以外的其他方法来增加胎儿肺容量。结果还表明，与对照动物相比，治疗胎儿的胶原蛋白到弹性蛋白的浓度增加了 11%（P < 0.01），表明肺结缔组织发生了变化。对空气固定充气肺进行的形态测量研究表明，与对照动物相比，治疗动物每单位体积肺的肺泡数量减少（0.95 × 0.07 × 106）（1.19 × 0.08 × 106；P < 0.025），并且与对照动物相比，治疗动物的肺平均表面积减少（506 × 10 cm2 / cm3） （561 × 9 cm2/cm3；P < 0.005）。这些发现表明，最大肺容量的增加至少部分与肺泡扩张性的增加有关。总之，这些压力容积研究结果、生化研究和形态测量分析表明，倍他米松对恒河猴胎肺的主要影响是改变肺结缔组织特征。在该恒河猴胎儿模型中，肺表面活性物质的变化似乎功能意义较小。这些研究结果与其他动物研究之间的差异可能是由于物种、制剂或糖皮质激素给药方法的差异所致。推测：母体倍他米松治疗会改变发育中胎儿肺的结缔组织特性，这可能对肺机械特性产生长期影响。
Summary: Pregnant rhesus monkeys (Macaca mulatta) at 67 to 85% of term pregnancy were treated with betamethasone for 3 days and then delivered by cesarean section. These treated fetuses had larger lung volumes (32.6 × 1.8 ml/kg of body weight) compared to gestational age-matched controls (22.9 × 3.2 ml/kg of body weight; P < 0.025) but no alterations in surfactant properties as measured by amniotic fluid L/S ratios, alveolar deflation stability, or lung phosphatidylcholine. These findings suggest that betamethasone effects an increase in fetal lung volume by some method other than alteration in alveolar surfactant concentrations. Results also demonstrated an 11% increase in the collagen to elastin concentration in the treated fetuses as compared to the control animals (P < 0.01), suggesting alterations in lung connective tissue. Morphometric studies done on the air-fixed inflated lung demonstrated a decrease in the number of alveoli per unit volume of lung among the treated animals (0.95 × 0.07 × 106) compared to the control animals (1.19 × 0.08 × 106; P < 0.025) and a reduction in the mean surface area of the lungs of the treated animals (506 × 10 cm2 per cm3) compared to the control animals (561 × 9 cm2 per cm3; P < 0.005). These findings suggest that at least part of the increased maximal lung volumes is related to increased alveolar distensibility. Together, these pressure volume findings, biochemical studies, and morphometric analyses indicate that a major effect of betamethasone on the rhesus fetal lung is to alter lung connective tissue characteristics. Alterations in lung surfactant appear to be of less functional significance in this rhesus fetal model. The disparity between these findings and other animal studies might be due to differences in species, the preparation, or the method of glucocorticoid administration.Speculation: Maternal betamethasone treatment produces alterations in the connective tissue properties of the developing fetal lung, which could have long-lasting effects on lung mechanical properties.