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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 摘要：产前类固醇现在通常用于照顾那些有早产迹象或有早产风险因素的妇女。 众所周知，这些产前类固醇刺激肺发育和表面活性物质的产生，出生时肺成熟度的增加至少部分地导致类固醇治疗的早产儿呼吸窘迫综合征（RDS）的发生率降低。 然而，这些类固醇对胎儿，青少年和成人骨骼肌的影响的研究表明，成熟和功能的骨骼肌可能会受到产前类固醇暴露的影响。 因此，本研究的目的是确定产前类固醇治疗对豚鼠骨骼肌发育的影响。 我们建议测试的假设，产前类固醇导致的变化（1）纤维类型的配置文件，（2）肌球蛋白重链（MHC）的表达模式，（3）纤维的大小，（4）豚鼠（Cavia porcellus）消化肌的功能能力。 妊娠47天时，将对妊娠Hartley（Crl：（HA）BR）豚鼠肌内注射倍他米松（0.5 mg/kg体重）或生理盐水两次（间隔24小时）。 最后一次注射后24小时分娩胎仔。 将使用组织化学和免疫细胞化学方法比较类固醇治疗和未治疗婴儿的6种痉挛肌的纤维类型分布和MHC亚型表达模式，以确定产前类固醇暴露是否导致快缩纤维百分比和发育肌球蛋白表达降低。 将测量纤维直径以确定betastatin是否导致萎缩。 为了确定治疗肌肉的功能能力是否受到精神上的影响，将测量组成这些肌肉的纤维的最大强直力（每横截面积）和最大无负荷缩短速度。早产儿经治疗的呼吸肌可能无法提供足够的呼吸动力，功能能力的下降可能导致产前类固醇暴露新生儿的进一步呼吸并发症。 如果这项研究表明，在倍他米松治疗的肌肉有形态学变化，这些变化导致这些肌肉快速收缩和产生力量的能力下降，这些发现将对新生儿出生后的治疗和支持产生影响。