Mehls O, Ritz E, Hunziker E B, Eggli P, Heinrich U, Zapf J
Department of Pediatrics, University of Heidelberg, Federal Republic of Germany.
Kidney Int. 1988 Jan;33(1):45-52. doi: 10.1038/ki.1988.7.
We compared growth rate, food conversion ratio and morphology of the growth zone in female Sprague-Dawley rats with subtotal nephrectomy or sham operation. Both groups were either given vehicle or 1.4 IU/day recombinant human growth hormone (GH) by s.c. osmotic minipump, or 2.5 IU twice daily intraperitoneally for 14 or 20 days, respectively. Compared to uremic rats infused with vehicle, infusion of GH significantly (P less than 0.01) improved growth; that is, it increased gain of weight (delta 27.0 +/- 7.7 g vs. 11.6 +/- 4.9 g) and length (delta 1.8 +/- 0.3 cm vs. 1.12 +/- 0.44 cm) in ad libitum fed uremic rats. This was accompanied by increased food utilization ratio (0.146 vs. 0.065 g weight gain per g food intake). A similar increment of growth and food utilization ratio was also observed in GH versus solvent infused controls, either pairfed as for the uremic animals or fed ad libitum. Despite administration of GH, growth was not completely restored to normal in uremic animals. Circulating immunoreactive IGF I was not significantly increased by GH infusion in either uremic animals or controls. Histological analyses of the proximal tibia showed increased rate of longitudinal growth, as evaluated by tetracyclin-labeling, and increased volumetric density of primary spongiosa with unchanged width of primary spongiosa trabecules when GH was infused in uremic animals. The data suggest that growth impairment in the uremic rat is partially responsive to GH, and this is not accompanied by an increase of circulating IGF I. Therapeutic trials with recombinant GH in uremic children appear justified.
我们比较了接受次全肾切除术或假手术的雌性Sprague-Dawley大鼠的生长速率、食物转化率和生长区形态。两组大鼠分别通过皮下渗透微型泵给予溶剂或1.4 IU/天的重组人生长激素(GH),或分别每天腹腔注射2.5 IU,共14天或20天。与输注溶剂的尿毒症大鼠相比,输注GH显著(P<0.01)改善了生长;也就是说,在自由进食的尿毒症大鼠中,GH增加了体重增加量(分别为27.0±7.7 g和11.6±4.9 g)和体长(分别为1.8±0.3 cm和1.12±0.44 cm)。这伴随着食物利用率的提高(每克食物摄入量的体重增加量分别为0.146和0.065 g)。在GH组与输注溶剂的对照组中,无论是像尿毒症动物那样配对喂养还是自由进食,都观察到了生长和食物利用率的类似增加。尽管给予了GH,但尿毒症动物的生长并未完全恢复正常。在尿毒症动物或对照组中,输注GH均未显著增加循环中的免疫反应性IGF I。对胫骨近端的组织学分析显示,在尿毒症动物中输注GH时,通过四环素标记评估的纵向生长速率增加,初级海绵质的体积密度增加,而初级海绵质小梁的宽度不变。数据表明,尿毒症大鼠的生长受损对GH有部分反应,且这并未伴随着循环中IGF I的增加。对尿毒症儿童进行重组GH的治疗试验似乎是合理的。