Hanna J D, Santos F, Foreman J W, Chan J C, Han V K
Department of Pediatrics, Medical College of Georgia, Augusta, USA.
Kidney Int. 1995 May;47(5):1374-82. doi: 10.1038/ki.1995.193.
To identify the molecular mechanisms involved in long bone growth of uremic animals, we evaluated the effects of recombinant human growth hormone (rhGH) supplementation on whole body growth, growth plate morphometrics, and insulin-like growth factor-I (IGF-I) gene expression in the tibial epiphyseal growth plates of uremic rats. Uremia was induced by a two-stage subtotal nephrectomy (Nx) of 30-day-old rats, followed by rhGH (N = 6) or saline (N = 6) treatment from day 56 to day 70 of age. Controls (N = 4) were sham decapsulated. Treatment with rhGH on Nx animals caused: (1) a significant increase in weight, (2) longitudinal growth similar to controls, and (3) increased total growth plate width predominantly due to an increase in hypertrophic zone width. rhGH increased IGF-I mRNA abundance in both zones, but the increase was greater in the proliferative zone. These changes were accompanied by concomitant alterations in IGF-I immunoreactivity. In uremic animals, therefore, rhGH treatment induces local IGF-I gene expression in the growth plate and increases the hypertrophic zone width but not the proliferative zone width. The latter suggests resistance to IGF-I action in that zone.
为了确定参与尿毒症动物长骨生长的分子机制，我们评估了补充重组人生长激素（rhGH）对尿毒症大鼠胫骨骨骺生长板的全身生长、生长板形态计量学以及胰岛素样生长因子-I（IGF-I）基因表达的影响。通过对30日龄大鼠进行两阶段次全肾切除术（Nx）诱导尿毒症，然后在56日龄至70日龄期间对大鼠进行rhGH（N = 6）或生理盐水（N = 6）治疗。对照组（N = 4）进行假去包膜手术。对Nx动物用rhGH治疗导致：（1）体重显著增加，（2）纵向生长与对照组相似，（3）总生长板宽度增加，主要是由于肥大区宽度增加。rhGH使两个区域的IGF-I mRNA丰度增加，但在增殖区增加更大。这些变化伴随着IGF-I免疫反应性的相应改变。因此，在尿毒症动物中，rhGH治疗诱导生长板中局部IGF-I基因表达并增加肥大区宽度，但不增加增殖区宽度。后者表明该区域对IGF-I作用有抗性。
