Kovàcs G, Fine R N, Worgall S, Schaefer F, Hunziker E B, Skottner-Lindun A, Mehls O
Division Pediatric Nephrology, University Children's Hospital, Heidelberg, Germany.
Kidney Int. 1991 Dec;40(6):1032-40. doi: 10.1038/ki.1991.311.
Treatment with supraphysiological doses of corticosteroids results in protein wasting and impairment of growth, whereas exogenous growth hormone (GH) causes anabolism and improvement of growth. We wanted to know whether the growth depressing effects of methylprednisolone (MP) are more expressed in an organism which is chronically diseased and whether these effects can be counterbalanced by concomitant treatment with recombinant human growth hormone (rhGH). MP in doses from 1 to 9 mg/kg/day caused a dose dependent reduction of length gain, weight gain and weight gain/food intake ratio in 140 g healthy female Sprague-Dawley rats. Food intake was not affected by MP. This points to a change in food metabolism as a mechanism for growth impairment. In addition, treatment with MP inhibited endogenous GH secretion, documented by serum GH concentration profiles over seven hours, decreased IGF-1 serum concentration and disturbed growth cartilage plate architecture. Concomitant treatment with 2.5 to 20 IU/rhGH/kg/day prevented the negative effects of MP on growth in a dose dependent manner and normalized growth plate architecture. In uremic rats in which food efficiency and growth was already reduced, 6 mg MP/kg/day further decreased length gain and prevented weight gain completely by bringing the weight gain/food conversion ratio to the nadir. All effects of MP including reduction of muscle mass could be prevented by concomitant treatment with 10 IU rhGH/kg/day. The effects of MP and rhGH on food efficiency and growth in uremic animals were numerically nearly identical to those in pair fed ad libitum fed controls, but this may be more relevant in the diseased organism in which basal growth is already suppressed.
用超生理剂量的皮质类固醇进行治疗会导致蛋白质消耗和生长受损,而外源性生长激素(GH)则会引起合成代谢并促进生长。我们想了解甲泼尼龙(MP)对生长的抑制作用在慢性疾病机体中是否表现得更明显,以及这些作用是否可以通过同时给予重组人生长激素(rhGH)来抵消。在140g健康雌性Sprague-Dawley大鼠中,剂量为1至9mg/kg/天的MP导致身长增加、体重增加和体重增加/食物摄入量比值呈剂量依赖性降低。食物摄入量不受MP影响。这表明食物代谢的改变是生长受损的一种机制。此外,MP治疗抑制了内源性GH分泌,这通过7小时的血清GH浓度曲线得到证实,降低了IGF-1血清浓度,并扰乱了生长软骨板结构。同时给予2.5至20IU/rhGH/kg/天可剂量依赖性地预防MP对生长的负面影响,并使生长板结构正常化。在食物利用率和生长已经降低的尿毒症大鼠中,6mg MP/kg/天进一步降低了身长增加,并通过使体重增加/食物转化率降至最低点而完全阻止了体重增加。MP的所有作用,包括肌肉量减少,都可以通过同时给予10IU rhGH/kg/天来预防。MP和rhGH对尿毒症动物食物利用率和生长的影响在数值上与随意进食的配对对照动物几乎相同,但这在基础生长已经受到抑制的患病机体中可能更具相关性。