Wimalawansa S M, Chapa M T, Wei J N, Westlund K N, Quast M J, Wimalawansa S J
Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555-1065, USA.
J Appl Physiol (1985). 1999 Jun;86(6):1841-6. doi: 10.1152/jappl.1999.86.6.1841.
Microgravity causes rapid decrement in musculoskeletal mass is associated with a marked decrease in circulatory testosterone levels, as we reported in hindlimb-suspended (HLS) rats. In this model which simulates microgravity, we hypothesized that testosterone supplementation should prevent these losses, and we tested this in two studies. Muscle volumes and bone masses were quantitated by using magnetic resonance imaging (MRI) on day 12. In the first study, 12-wk-old Sprague-Dawley rats that were HLS for 12 days lost 28.5% of muscle volume (53.3 +/- 4.8 vs. 74.5 +/- 3.6 cm3 in the ground control rats; P < 0.001) and had a 5% decrease in bone mineral density (BMD) (P < 0.05). In the second study, 30 male 12-wk-old Wistar rats were HLS and were administered either a vehicle (control), testosterone, or nandrolone decanoate (ND). An additional 20 rats were used as ground controls, one-half of which received testosterone. HLS rats had a significant reduction in muscle volume (42.9 +/- 3.0 vs. 56 +/- 1.8 cm3 in ground control rats; P < 0.01). Both testosterone and ND treatments prevented this muscle loss (51.5 +/- 2 and 51.6 +/- 1.2 cm3, respectively; a 63% improvement; P < 0. 05). There were no statistical differences between the two active treatment groups nor with the ground controls. Similarly, there was an 85% improvement in BMD in the testosterone group (1.15 +/- 0.04 vs. 1.04 +/- 0.04 density units in vehicle controls; P < 0.05) and a 76% improvement in the ND group (1.13 +/- 0.07 density units), whereas ground control rats had a BMD of 1.17 +/- 0.03 density units. Because serum testosterone levels are markedly reduced in this model of simulated microgravity, androgen replacement seems to be a rational countermeasure to prevent microgravity-induced musculoskeletal losses.
正如我们在大鼠后肢悬吊（HLS）实验中所报道的，微重力会导致肌肉骨骼质量迅速下降，这与循环睾酮水平的显著降低有关。在这个模拟微重力的模型中，我们假设补充睾酮可以预防这些损失，并在两项研究中进行了验证。在第12天，通过磁共振成像（MRI）对肌肉体积和骨质量进行定量分析。在第一项研究中，12周龄的Sprague-Dawley大鼠进行12天的后肢悬吊后，肌肉体积减少了28.5%（与地面对照大鼠相比，分别为53.3±4.8 vs. 74.5±3.6 cm³；P<0.001），骨矿物质密度（BMD）下降了5%（P<0.05）。在第二项研究中，30只12周龄的雄性Wistar大鼠进行后肢悬吊，并分别给予载体（对照）、睾酮或癸酸诺龙（ND）。另外20只大鼠作为地面对照，其中一半接受睾酮治疗。后肢悬吊大鼠的肌肉体积显著减少（与地面对照大鼠相比，分别为42.9±3.0 vs. 56±1.8 cm³；P<0.01）。睾酮和ND治疗均能预防这种肌肉损失（分别为51.5±2和51.6±1.2 cm³；改善了63%；P<0.05）。两个活性治疗组之间以及与地面对照组之间均无统计学差异。同样，睾酮组的骨矿物质密度提高了85%（与载体对照组相比，分别为1.15±0.04 vs. 1.04±0.04密度单位；P<0.05），ND组提高了76%（1.13±0.07密度单位），而地面对照大鼠的骨矿物质密度为1.17±0.03密度单位。由于在这个模拟微重力模型中血清睾酮水平显著降低，雄激素替代似乎是预防微重力引起的肌肉骨骼损失的合理对策。
