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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 产前类固醇通常用于护理有早产迹象或有早产危险因素的妇女。 这些类固醇刺激早产儿的肺部发育，从而降低死亡率。 我们的工作表明，多次注射倍他米松（妊娠 65%、75% 和 85% 时每周注射 2 次）会导致豚鼠胎儿的慢肌纤维和快肌纤维的氧化能力增加（Cavia porcellus）斜角肌，一种辅助吸气肌。 因此，本研究的目的是检查产前类固醇暴露（单次（妊娠 70% 时注射 2 次）和多疗程）对豚鼠呼吸肌代谢和功能特性的影响。 我们建议测试以下假设：产前类固醇会导致五只豚鼠通气肌的（1）氧化能力和（2）抗疲劳能力发生变化。 根据所提出的单程和多程注射方案，对怀孕豚鼠肌内注射倍他米松（0.5 mg/kg体重）或无菌水。 胎儿将在最后一次注射后 24 小时分娩，并采集呼吸肌样本。 将使用组织和免疫细胞化学方法来比较类固醇中的（1）慢肌纤维和快肌纤维中的 NADH-四唑还原酶活性和（2）通气肌的毛细血管密度（每个纤维横截面积的毛细血管数量） - 治疗和未治疗的胎儿以确定产前类固醇暴露是否会导致这两种氧化能力指标的增加。 还将通过生化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能力。 如果接受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能力，这些肌肉将更好地支持早产儿的通气需求。 公共健康相关性：产前类固醇通常给予有早产迹象或有早产危险因素的妇女，众所周知，它可以加速胎儿肺部发育，使早产的新生儿呼吸更顺畅。 虽然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维持通气所需的代谢机制的获得，从而更好地为他们在子宫外的生活做好准备。