胰岛素样生长因子-1对慢性肾功能不全大鼠骨骼肌蛋白质合成与分解的影响
作者：高秀林
单位：首都医科大学附属复兴医院 肾内科
关键词：
中国临床营养杂志000112摘 要：目的探讨胰岛素样生长因子(IGF-1)，在CRF大鼠及配对喂养的假手术(ShamOperated，SO)对照组大鼠骨骼肌蛋白质代谢上的作用。 方法从两组大鼠血清和骨骼肌中提取IGF-1，用放射免疫分析法测定血清及骨骼肌中的IGF-1水平；用荧光测定法检测肱骨内上髁肌培养液中总酪氨酸的浓度，进而计算基础蛋白合成率及分解率。通过剂量反应试验，观察不同浓度重组人类胰岛素样生长因子-1(rhIGF-1)对骨骼肌蛋白质合成与分解的影响。 结果CRF大鼠血清IGF-1浓度显著低于SO对照大鼠(170.3±16.4比410.4±49.3ng/ml)，骨骼肌IGF-1含量也明显低于SO组(4.22±1.03比6.93±1.4lng/g)，P值均<0.001。CRF组大鼠肱骨内上髁肌的基础蛋白合成串(24.0±2.1nmol酪氨酸·g肌肉-1·h-1)比SO组(30.8±2.4nmol酪氨酸·g肌肉-1·h-1)低22%，P<0.05。而基础蛋白分解率则比SO组高78%(234.4±13.8比131.7±8.4nmol酪氨酸·g肌肉-1.h-1，P<0.001。剂量反应试验发现，rhlGF-1对CRF大鼠骨骼肌蛋白质合成和分解的作用明显低于SO大鼠。浓度为25-500ng/ml的rhlGF-1对CRF大鼠蛋白质合成的促进作用仅为SO大鼠的25%～44%，对蛋白质分解的抑制作用仅为对照组的15%～42%。说明CRF大鼠骨骼肌对rhlGF-1促进蛋白质合成代谢的反应性降低。 结论CRF时血清及骨骼肌的IGF-1含量减少，骨骼肌对IGF-1促进蛋白质合成代谢的作用存在抵抗，这些可能是CRF患者骨骼肌蛋白质合成减少、分解增强，进而导致营养不良、肌肉萎缩的主要原因。
, 百拇医药
The influence of insulin-like growth factor 1 on protein synthesis and degradation in skeletal muscle of rats with chronic renal failure
GAO Xiulin
(Division of Nephrology, Fuzing Hospital, Beijing 100038)
Abstract：Objective Patients with chronic renal failure (CRF) are frequently malnourished, skeletal muscle atrophy and protein depleted. Insulin-like growth factor 1 (IGF-1) is an anabolic hormone. The actions of IGF-1 on protein turnover were examined in skeletal muscle of rats with CRF and sham operated (SO), pair-fed controls. IGF-1 was extracted from serum and skeletal muscle and then measured by radio-immunoassay (RIA). Total tyrosine in the supernatant from the medium was measured fluorometrically and then basal protein synthesis rate and degradation rate in skeletal muscle were calculated. The results showed that IGF-1 levels in serum and in skeletal muscle in the CRF rats were 170.3 ± 16.4 ng/ml and 4.22 ± 1.03ng/grams respectively. These values were significantly lower than in the SO rats (410.4 ± 49.3ng/ml in serum and 6.93 + 1.41ng/grams in muscle, respectively, P<0.001 for each comparison). The basal protein synthesis rate in epitrochlearis muscle of the CRF rats (24.0 ± 2.1 nmol Tyr/grams per hour ) was significantly lower, by 22%, than that of SO, pair-fed rats (30.8 ± 2.4nmol Tyr/grams per hour,P<0.05). In contrast, the basal protein degradation rate in the epitrochlearis muscle of the CRF rats (234.4 ± 13.8nmol Tyr/grams per hour) was increased by 78% in comparison to SO rats (131.7 ± 8.4nmol Tyr/grams per hour, P< 0.001). Dose response curves of rhIGF-1 showed that the effects of rhIGF-1 On muscle protein synthesis and degradation in CRF rats were markedly attenuated as compared to their SO pair-fed controls. The enhancement in protein synthesis induced by increasing concentrations of rhIGF-1 (ranging from 25 to 500ng/ml) in CRF rats was only 25 to 44% of that in SO rats. Similarly, the suppressive effects of the various concentrations of rhlGF-1 on protein degradation in muscle from CRF rats were only 15 to 42% of those found in SO rats. These data indicate that there are impaired actions of rhIGF-1 on protein synthesis and degradation in skeletal muscle of rats with CRF. These findings suggest that the decreased IGF-1 levels in serum and in skeletal muscle, the resistance to the anabolie effects of IGF-1 on protein metabolism may be the main causes of reduced protein synthesis and enhaneed protein degradation in muscle, muscle atrophy and malnutrition in patients with CRF., 百拇医药
单位：首都医科大学附属复兴医院 肾内科
关键词：
中国临床营养杂志000112摘 要：目的探讨胰岛素样生长因子(IGF-1)，在CRF大鼠及配对喂养的假手术(ShamOperated，SO)对照组大鼠骨骼肌蛋白质代谢上的作用。 方法从两组大鼠血清和骨骼肌中提取IGF-1，用放射免疫分析法测定血清及骨骼肌中的IGF-1水平；用荧光测定法检测肱骨内上髁肌培养液中总酪氨酸的浓度，进而计算基础蛋白合成率及分解率。通过剂量反应试验，观察不同浓度重组人类胰岛素样生长因子-1(rhIGF-1)对骨骼肌蛋白质合成与分解的影响。 结果CRF大鼠血清IGF-1浓度显著低于SO对照大鼠(170.3±16.4比410.4±49.3ng/ml)，骨骼肌IGF-1含量也明显低于SO组(4.22±1.03比6.93±1.4lng/g)，P值均<0.001。CRF组大鼠肱骨内上髁肌的基础蛋白合成串(24.0±2.1nmol酪氨酸·g肌肉-1·h-1)比SO组(30.8±2.4nmol酪氨酸·g肌肉-1·h-1)低22%，P<0.05。而基础蛋白分解率则比SO组高78%(234.4±13.8比131.7±8.4nmol酪氨酸·g肌肉-1.h-1，P<0.001。剂量反应试验发现，rhlGF-1对CRF大鼠骨骼肌蛋白质合成和分解的作用明显低于SO大鼠。浓度为25-500ng/ml的rhlGF-1对CRF大鼠蛋白质合成的促进作用仅为SO大鼠的25%～44%，对蛋白质分解的抑制作用仅为对照组的15%～42%。说明CRF大鼠骨骼肌对rhlGF-1促进蛋白质合成代谢的反应性降低。 结论CRF时血清及骨骼肌的IGF-1含量减少，骨骼肌对IGF-1促进蛋白质合成代谢的作用存在抵抗，这些可能是CRF患者骨骼肌蛋白质合成减少、分解增强，进而导致营养不良、肌肉萎缩的主要原因。
, 百拇医药
The influence of insulin-like growth factor 1 on protein synthesis and degradation in skeletal muscle of rats with chronic renal failure
GAO Xiulin
(Division of Nephrology, Fuzing Hospital, Beijing 100038)
Abstract：Objective Patients with chronic renal failure (CRF) are frequently malnourished, skeletal muscle atrophy and protein depleted. Insulin-like growth factor 1 (IGF-1) is an anabolic hormone. The actions of IGF-1 on protein turnover were examined in skeletal muscle of rats with CRF and sham operated (SO), pair-fed controls. IGF-1 was extracted from serum and skeletal muscle and then measured by radio-immunoassay (RIA). Total tyrosine in the supernatant from the medium was measured fluorometrically and then basal protein synthesis rate and degradation rate in skeletal muscle were calculated. The results showed that IGF-1 levels in serum and in skeletal muscle in the CRF rats were 170.3 ± 16.4 ng/ml and 4.22 ± 1.03ng/grams respectively. These values were significantly lower than in the SO rats (410.4 ± 49.3ng/ml in serum and 6.93 + 1.41ng/grams in muscle, respectively, P<0.001 for each comparison). The basal protein synthesis rate in epitrochlearis muscle of the CRF rats (24.0 ± 2.1 nmol Tyr/grams per hour ) was significantly lower, by 22%, than that of SO, pair-fed rats (30.8 ± 2.4nmol Tyr/grams per hour,P<0.05). In contrast, the basal protein degradation rate in the epitrochlearis muscle of the CRF rats (234.4 ± 13.8nmol Tyr/grams per hour) was increased by 78% in comparison to SO rats (131.7 ± 8.4nmol Tyr/grams per hour, P< 0.001). Dose response curves of rhIGF-1 showed that the effects of rhIGF-1 On muscle protein synthesis and degradation in CRF rats were markedly attenuated as compared to their SO pair-fed controls. The enhancement in protein synthesis induced by increasing concentrations of rhIGF-1 (ranging from 25 to 500ng/ml) in CRF rats was only 25 to 44% of that in SO rats. Similarly, the suppressive effects of the various concentrations of rhlGF-1 on protein degradation in muscle from CRF rats were only 15 to 42% of those found in SO rats. These data indicate that there are impaired actions of rhIGF-1 on protein synthesis and degradation in skeletal muscle of rats with CRF. These findings suggest that the decreased IGF-1 levels in serum and in skeletal muscle, the resistance to the anabolie effects of IGF-1 on protein metabolism may be the main causes of reduced protein synthesis and enhaneed protein degradation in muscle, muscle atrophy and malnutrition in patients with CRF., 百拇医药