EFFECTS OF PRENATAL STEROID TREATMENT ON GUINEA PIG VENTILATORY MUSCLES

产前类固醇治疗对豚鼠通气肌的影响

• 批准号: 8168098
• 负责人: JENNIFER L DEAROLF
• 金额: $ 13.58万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-19 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8168098
• 关键词: Activities of Daily Living; Adolescent; Adult; Affect; Area; Atrophic; Betamethasone; Birth; Body Weight; Breathing; Caliber; Caring; Cavia; Cavia porcellus; Computer Retrieval of Information on Scientific Projects Database; Contracts; Development; Fetus; Fiber; Funding; Grant; Hour; Incidence; Infant; Injection of therapeutic agent; Institution; Lead; Lung; Measures; Methods; Muscle; Myosin ATPase; Myosin Heavy Chains; Pattern; Pregnancy; Premature Infant; Production; Protein Isoforms; Research; Research Personnel; Resources; Respiratory Muscles; Risk Factors; Saline; Skeletal Muscle; Source; Steroids; Testing; United States National Institutes of Health; Woman; abstracting; fetal; lung development; neonate; pregnant; prenatal; respiratory; respiratory distress syndrome; surfactant

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Abstract: Prenatal steroids are now routinely used in the care of women that show signs or have risk factors for giving birth to their fetuses prematurely. It is known that these prenatal steroids stimulate lung development and surfactant production and that the increased maturity of the lungs at birth is at least partially responsible for the decreased incidence of respiratory distress syndrome (RDS) in steroid-treated premature infants. However, studies of the effects of these steroids on fetal, juvenile, and adult skeletal muscle suggest that the maturation and function of the ventilatory muscles may be detrimentally affected by prenatal steroid exposure. Therefore, the purpose of this study is to determine the effects of prenatal steroid treatment on the development of guinea pig ventilatory muscles. We propose to test the hypotheses that prenatal steroids lead to changes in (1) the fiber type profiles, (2) myosin heavy chain (MHC) expression patterns, (3) fiber sizes, and (4) the functional abilities of guinea pig (Cavia porcellus) ventilatory muscles. Pregnant Hartley (Crl:(HA)BR) guinea pigs will be injected twice (24 hours apart) intramuscularly with betamethasone (0.5 mg/kg body weight) or saline at forty-seven days gestation. The fetuses will then be delivered 24 hours after the final injection. Histochemical and immunocytochemical methods will be used to compare the fiber type profiles and MHC isoform expression patterns of six ventilatory muscles in steroid treated and untreated infants to determine if prenatal steroid exposure leads to decreases in the percentages of fast-twitch fibers and in the expression of developmental myosins. Fiber diameters will be measured to determine if betamethasone leads to atrophy. To determine if the functional abilities of treated muscles are detrimentally affected, the maximum tetanic forces (per cross-sectional area) and maximal unloaded shortening velocities of the fibers making up these muscles will be measured. The treated ventilatory muscles of premature infants may not be able to adequately power breathing, and the decreases in functional abilities may lead to further respiratory complications in prenatal steroid exposed neonates. If this study demonstrates that there are morphological changes in the betamethasone-treated muscles and that these changes lead to decreases in the abilities of these muscles to contract quickly and produce force, these findings will have implications for the treatment and support of neonates after they are born.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 摘要：产前类固醇现在常规用于护理有早产迹象或有早产危险因素的妇女。 众所周知，这些产前类固醇会刺激肺部发育和表面活性剂的产生，并且出生时肺部成熟度的提高至少部分是类固醇治疗的早产儿呼吸窘迫综合征（RDS）发生率降低的原因。 然而，对这些类固醇对胎儿、青少年和成人骨骼肌影响的研究表明，通气肌的成熟和功能可能会受到产前类固醇暴露的不利影响。 因此，本研究的目的是确定产前类固醇治疗对豚鼠通气肌发育的影响。 我们建议测试以下假设：产前类固醇导致豚鼠的（1）纤维类型特征、（2）肌球蛋白重链（MHC）表达模式、（3）纤维大小和（4）功能能力发生变化。 Cavia porcellus）通气肌。 怀孕 Hartley (Crl:(HA)BR) 豚鼠将在妊娠 47 天时肌内注射倍他米松（0.5 mg/kg 体重）或盐水两次（间隔 24 小时）。 最后一次注射后 24 小时，胎儿就会分娩。 将使用组织化学和免疫细胞化学方法来比较类固醇治疗和未治疗婴儿的六种通气肌的纤维类型概况和 MHC 同工型表达模式，以确定产前类固醇暴露是否会导致快肌纤维百分比和表达的减少。发育性肌球蛋白。 将测量纤维直径以确定倍他米松是否导致萎缩。 为了确定治疗肌肉的功能是否受到不利影响，将测量构成这些肌肉的纤维的最大强直力（每个横截面积）和最大空载缩短速度。早产儿经过治疗的通气肌可能无法为呼吸提供足够的动力，并且功能能力的下降可能会导致产前接触类固醇的新生儿出现进一步的呼吸系统并发症。 如果这项研究证明倍他米松治疗的肌肉存在形态变化，并且这些变化导致这些肌肉快速收缩和产生力量的能力下降，那么这些发现将对新生儿出生后的治疗和支持产生影响。出生。