Logan J L, Benson B
Renal Section, V.A. Medical Center, Tucson, AZ 85723.
Transplantation. 1987 Oct;44(4):559-62. doi: 10.1097/00007890-198710000-00020.
Renal transplantation or a partial reduction in renal mass prompts compensatory growth of the kidney, an event that appears to be stimulated by a circulating substance, the purported renotropic factor. This factor may stimulate synthesis of renal polyamines by induction of the rate-limiting enzyme in polyamine metabolism, ornithine decarboxylase. Cyclosporine has been shown to attenuate induction of renal ornithine decarboxylase activity in response to other tropic hormones, such as prolactin, thyroxine, and dexamethasone. These studies were undertaken to evaluate the effects of cyclosporine on induction of renal ornithine decarboxylase activity and growth in response to the serum renotropic factor. Rats were given either 15.0 or 25.0 mg/kg/day or cyclosporine for six days following removal of one kidney. The growth of the remaining kidney was reduced by cyclosporine treatment compared with pair-fed, vehicle-treated control animals. Administration of 25.0 mg/kg/day of cyclosporine also reduced the activity of ornithine decarboxylase in the growing kidney. We conclude that cyclosporine imposes a limitation on the ability of the kidney to grow in response to a reduction in renal mass in rats. The mechanisms of this effect may relate to a blunting of the induction of renal ornithine decarboxylase activity in response to the renotropic factor.
肾移植或部分肾切除可促使肾脏发生代偿性生长,这一过程似乎受一种循环物质(即所谓的促肾生长因子)刺激。该因子可能通过诱导多胺代谢中的限速酶鸟氨酸脱羧酶来刺激肾多胺的合成。已表明环孢素可减弱肾脏对其他促生长激素(如催乳素、甲状腺素和地塞米松)的反应,从而降低鸟氨酸脱羧酶的诱导作用。开展这些研究是为了评估环孢素对血清促肾生长因子诱导的肾鸟氨酸脱羧酶活性及肾脏生长的影响。切除一侧肾脏后,给大鼠连续6天给予15.0或25.0mg/kg/天的环孢素。与配对喂养、给予赋形剂处理的对照动物相比,环孢素处理使剩余肾脏的生长减缓。给予25.0mg/kg/天的环孢素也降低了生长中肾脏的鸟氨酸脱羧酶活性。我们得出结论,环孢素限制了大鼠肾脏在肾质量减少时的生长能力。这种作用机制可能与肾鸟氨酸脱羧酶活性对促肾生长因子诱导的减弱有关。