EFFECTS OF PRENATAL STEROIDS ON THE FATIGUE PROPERTIES OF BREATHING MUSCLES

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 产前类固醇通常用于照顾有早产迹象或有早产风险因素的妇女。 这些类固醇刺激早产儿的肺发育，导致死亡率降低。 我们的工作表明，暴露于多疗程注射（每周2次注射，妊娠65%，75%和85%）的betastrin导致胎儿豚鼠（Cavia porcellus）斜角肌（辅助吸气肌）的慢肌和快肌纤维的氧化能力增加。 因此，本研究的目的是检查产前类固醇暴露（单次（70%妊娠时注射2次）和多次）对豚鼠呼吸肌代谢和功能特性的影响。 我们建议测试的假设，产前类固醇导致的变化（1）氧化能力和（2）疲劳抵抗力的五个豚鼠骨骼肌。 根据所提供的单疗程和多疗程注射时间表，对妊娠豚鼠肌内注射倍他米松（0.5 mg/kg体重）或无菌水。 将在末次注射后24小时分娩胎仔，并采集呼吸肌样本。 将使用组织化学和免疫细胞化学方法比较类固醇处理和未处理胎儿的（1）慢缩和快缩纤维中的NADH-四唑还原酶活性和（2）痉挛肌的毛细血管密度（每纤维横截面积的毛细血管数量），以确定产前类固醇暴露是否导致这两种氧化能力指标增加。 还将通过生物化学方法测量全肌肉柠檬酸合酶（CS）活性，以评估产前类固醇是否会增加治疗肌肉中的CS活性水平。 最后，将确定这些肌肉的抗疲劳性。 如果经过处理的肌肉表达更多的氧化酶，更大的毛细血管密度和抗疲劳性，这些肌肉将更好地准备支持早产儿的排便需求。 公共卫生相关性：产前类固醇，常规给予有早产迹象或有早产风险因素的妇女，已知可加速胎儿肺发育，使新生儿在早产时呼吸更顺畅。 尽管皮质类固醇对成熟的骨骼肌有不利影响，但产前类固醇可能会加速这些早产儿获得维持通气所需的代谢机制，为他们在子宫外的生活做好更好的准备。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Prenatal steroids are routinely used in the care of women who show signs of or have risk factors for premature birth. These steroids stimulate lung development in premature infants, leading to decreased mortality rates. Our work has shown that exposure to a multi-course injection (2 injections/week at 65%, 75%, and 85% gestation) of betamethasone leads to increased oxidative capacities of the slow- and fast-twitch fibers of the fetal guinea pig (Cavia porcellus) scalenus, an accessory inspiratory muscle. Therefore, the purpose of this study is to examine the effects of prenatal steroid exposure, both single (2 injections at 70% gestation) and multi-course, on the metabolic and functional properties of guinea pig breathing muscles. We propose to test the hypotheses that prenatal steroids lead to changes in the (1) oxidative capacities and (2) fatigue resistance of five guinea pig ventilatory muscles. Pregnant guinea pigs will be injected intramuscularly with betamethasone (0.5 mg/kg of body weight) or sterile water according to the presented single and multi-course injection schedules. Fetuses will be delivered 24 hours after the final injection, and breathing muscle samples will be collected. Histo- and immunocytochemical methods will be used to compare the (1) NADH-tetrazolium reductase activities in slow- and fast-twitch fibers and (2) capillary densities (number of capillaries per fiber cross-sectional area) of the ventilatory muscles in steroid-treated and untreated fetuses to determine whether prenatal steroid exposure leads to increases in both of these measures of oxidative capacity. Whole-muscle citrate synthase (CS) activities will also be measured biochemically to assess whether prenatal steroids increase CS activity levels in treated muscles. Finally, the fatigue resistance of these muscles will be determined. If the treated muscles express more oxidative enzymes, greater capillary densities, and fatigue resistance, these muscles will be better prepared to support the ventilatory needs of premature infants. Public Health Relevance: Prenatal steroids, routinely given to women who show signs of or have risk factors for giving birth prematurely, are known to accelerate fetal lung development, allowing newborns to breathe more competently if they are born prematurely. Whereas corticosteroids have detrimental effects in mature skeletal muscle, prenatal steroids may accelerate the acquisition of the metabolic machinery necessary to sustain ventilation in these premature infants, better preparing them for life outside the womb.