EFFECTS OF PRENATAL STEROID TREATMENT ON GUINEA PIG VENTILATORY MUSCLES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 3.摘要：对于出现早产征兆或有早产危险因素的妇女，目前通常使用产前类固醇进行护理。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，出生时肺的成熟度增加至少是导致接受类固醇治疗的早产儿呼吸窘迫综合征(RDS)发生率下降的部分原因。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，产前接触类固醇可能会对呼吸肌的成熟和功能产生不利影响。因此，本研究的目的是确定产前激素治疗对豚鼠呼吸肌发育的影响。我们建议检验如下假设：产前类固醇导致(1)纤维类型变化，(2)肌球蛋白重链(MHC)表达模式，(3)纤维大小，(4)豚鼠(Cavia Porcellus)呼吸肌的功能能力改变。怀孕的Hartley(CRL：(HA)BR)豚鼠将在妊娠47天时两次(间隔24小时)肌肉注射倍他米松(0.5 mg/kg体重)或生理盐水。胎儿将在最后一次注射后24小时出生。我们将用组织化学和免疫细胞化学方法比较激素治疗和未治疗的婴儿六种呼吸肌的纤维类型和MHC亚型的表达模式，以确定产前激素暴露是否导致快速抽动纤维的百分比和发育肌球蛋白的表达减少。将测量纤维直径，以确定倍他米松是否会导致萎缩。为了确定治疗肌肉的功能能力是否受到不利影响，将测量组成这些肌肉的纤维的最大破伤力(每横截面积)和最大无负荷缩短速度。早产儿接受治疗的呼吸肌可能无法提供足够的呼吸动力，而功能能力的下降可能会导致产前接触类固醇的新生儿进一步出现呼吸系统并发症。如果这项研究表明，倍他米松治疗后的肌肉出现了形态变化，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，这些发现将对新生儿出生后的治疗和支持产生影响。

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. 3. 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.