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.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 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，导致死亡率降低。我们的工作表明，暴露于多疗程注射(65%、75%和85%孕期每周两次注射)的倍他米松可以增加胎鼠(Cavia Porcellus)斜角肌(一种辅助吸气肌)慢、快抽动纤维的氧化能力。因此，本研究的目的是探讨产前单次(70%孕期两次注射)和多次注射类固醇对豚鼠呼吸肌代谢和功能特性的影响。我们建议检验产前类固醇导致五种豚鼠呼吸肌的(1)氧化能力和(2)抗疲劳能力改变的假说。怀孕的豚鼠将按照所提出的单程和多疗程注射计划，肌肉注射倍他米松(0.5毫克/公斤体重)或无菌水。胎儿将在最后一次注射后24小时分娩，并将采集呼吸肌样本。组织化学和免疫细胞化学方法将被用来比较(1)NADH-四唑还原酶在慢和快收缩纤维中的活性和(2)呼吸肌的毛细血管密度(每纤维横截面积的毛细血管数量)，以确定产前激素暴露是否导致这两个指标的氧化能力的增加。整个肌肉的柠檬酸合成酶(CS)活性也将被生化测量，以评估产前类固醇是否增加了治疗肌肉中的CS活性水平。最后，将测定这些肌肉的疲劳抵抗力。如果经过处理的肌肉表现出更多的氧化酶、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呼吸需求。与公共卫生相关：通常会给有早产迹象或有早产风险因素的女性服用产前类固醇，众所周知，它会加速胎儿肺的发育，使新生儿在早产时呼吸更顺畅。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获得维持这些早产儿呼吸所需的代谢机制，更好地为他们在子宫外的生活做好准备。