EFFECTS OF PRENATAL STEROIDS ON THE FATIGUE PROPERTIES OF BREATHING MUSCLES

产前类固醇对呼吸肌疲劳特性的影响

• 批准号: 8359809
• 负责人: JENNIFER L DEAROLF
• 金额: $ 12.41万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8359809
• 关键词: Adrenal Cortex Hormones; Area; Arkansas; Betamethasone; Biomedical Research; Birth; Blood capillaries; Body Weight; Breathing; Caring; Cavia; Cavia porcellus; Citrate (si)-Synthase; Environmental air flow; Enzymes; Exposure to; Fatigue; Fetal Lung; Fetus; Fiber; Funding; Grant; Hour; Injection of therapeutic agent; Lead; Life; Measures; Metabolic; Methods; Muscle; NADH; National Center for Research Resources; Newborn Infant; Oxidoreductase; Pregnancy; Premature Birth; Premature Infant; Principal Investigator; Property; Research; Research Infrastructure; Resistance; Resources; Respiratory Muscles; Risk Factors; Sampling; Schedule; Skeletal Muscle; Source; Sterility; Steroids; Testing; Tetrazolium; United States National Institutes of Health; Uterus; Water; Woman; Work; capillary; cost; density; fetal; lung development; mortality; pregnant; prenatal; public health relevance

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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 产前类固醇通常用于护理表现出早产迹象或有危险因素的妇女。 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，β大厅的多道菜注射（妊娠65％，75％和85％的注射量为2次注射剂）会导致胎儿豚鼠（Cavia Porcellus）scalenus scalenus，一种辅助灵感效果的缓慢和快速交换纤维的氧化能力增加。 因此，这项研究的目的是检查产前类固醇暴露的影响，包括单次（妊娠70％的2次注射）和多道菜对豚鼠呼吸肌肉的代谢和功能特性。 我们建议测试假设产前类固醇会导致（1）氧化能力和（2）五只豚鼠通气肌的疲劳性变化。 根据提出的单一和多道菜注射时间表，将对怀孕的豚鼠注射肌内注射次米松（体重0.5 mg/kg体重）或无菌水。 胎儿将在最终注射后24小时交付，并收集呼吸肌肉样本。 组织和免疫细胞化学方法将用于比较缓慢和快速裂纹纤维中的（1）NADH四唑还原酶的活性，以及​​（2）毛细血管密度（每个光纤横断面的毛细血管次数）氧化能力。 全肌柠檬酸盐合酶（CS）活性还将以生物化度测量，以评估产前类固醇是否会增加处理过的肌肉中CS活性水平。 最后，将确定这些肌肉的疲劳性抗性。 如果治疗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，这些肌肉将为支持早产儿的通气需求做好准备。 公共卫生相关性：产前类固醇，通常给予表现出或有危险因素过早出生的妇女，众所周知，可以加速胎儿肺发育，如果他们过早出生，则可以更加能够呼吸。 尽管皮质类固醇对成熟的骨骼肌具有有害的影响，但产前类固醇可能会加速获得这些早产婴儿所必需的代谢机制，从而更好地为他们为子宫外的生活做准备。