Haramati A, Lumpkin M D, Mulroney S E
Department of Physiology and Biophysics, Georgetown University School of Medicine, Washington, District of Columbia 20007.
Am J Physiol. 1994 Apr;266(4 Pt 2):F628-32. doi: 10.1152/ajprenal.1994.266.4.F628.
Removal of one kidney results, within days, in accelerated growth of the remaining kidney. However, the mechanisms that underlie this compensatory renal hypertrophic response, particularly in the early time period following nephrectomy, are not understood. In this study we tested the hypothesis that removal of one kidney leads to a change in the pulsatile release of growth hormone (GH), which facilitates compensatory renal growth. Adult Wistar rats were implanted with Silastic cannulas in jugular veins and underwent either unilateral nephrectomy (UNX) or sham operation. Plasma levels of GH were determined 24 and 48 h after sham operation or UNX. Blood samples were taken every 20 min over a 6-h period from conscious, unrestrained animals. Pulsatile GH release was markedly elevated 24 h after UNX in both the amplitude of the surges as well as in the duration of release. Peak GH levels after 24 h were three- to fourfold higher in UNX rats compared with sham controls (417 +/- 75 vs. 119 +/- 23 ng/ml, P < 0.05). However, this enhanced release of GH appeared to be of short duration and began declining by 48 h post-UNX (peak level of 227 +/- 37 ng/ml, P < 0.05 vs. both 24 h UNX and sham controls). To examine whether this rise in GH release post-UNX contributed to the compensatory renal growth, rats underwent UNX and were immediately treated with an antagonist to GH-releasing factor (GRF-AN; i.e., [N-Ac-Tyr1,D-Arg2]GRF-(1-29) amide, 200 micrograms/kg twice daily), and the effects on GH release and renal growth were determined. Administration of GRF-AN significantly suppressed the increase in GH release post-UNX and was associated with a significant attenuation in renal growth 48 h post-UNX in GRF-AN-treated rats (8.7 +/- 2.6% vs. 22.7 +/- 3.0% in UNX controls, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
切除一侧肾脏会在数天内导致剩余肾脏加速生长。然而，这种代偿性肾肥大反应的潜在机制，尤其是在肾切除术后的早期阶段，尚不清楚。在本研究中，我们检验了这样一个假设：切除一侧肾脏会导致生长激素（GH）脉冲式释放发生变化，从而促进代偿性肾生长。成年Wistar大鼠在颈静脉植入硅橡胶套管，然后接受单侧肾切除术（UNX）或假手术。在假手术或UNX术后24小时和48小时测定血浆GH水平。在6小时内，每隔20分钟从清醒、不受约束的动物身上采集血样。UNX术后24小时，GH脉冲式释放的峰值以及释放持续时间均显著升高。与假手术对照组相比，UNX大鼠术后24小时的GH峰值水平高出三到四倍（417±75 vs. 119±23 ng/ml，P<0.05）。然而，这种增强的GH释放似乎持续时间较短，在UNX术后48小时开始下降（峰值水平为227±37 ng/ml，与UNX术后24小时和假手术对照组相比，P<0.05）。为了研究UNX术后GH释放的增加是否有助于代偿性肾生长，大鼠接受UNX手术，并立即用生长激素释放因子拮抗剂（GRF-AN；即[N-Ac-Tyr1,D-Arg2]GRF-(1-29)酰胺，200微克/千克，每日两次）进行治疗，然后测定其对GH释放和肾生长的影响。给予GRF-AN可显著抑制UNX术后GH释放的增加，并与GRF-AN治疗的大鼠在UNX术后48小时肾生长的显著减弱相关（8.7±2.6% vs. UNX对照组的22.7±3.0%，P<0.05）（摘要截断于250字）
