Ghahary A, Fu S, Shen Y J, Shankowsky H A, Tredget E E
Department of Surgery, University of Alberta, Edmonton, Canada.
Mol Cell Biochem. 1994 Jun 29;135(2):171-80. doi: 10.1007/BF00926520.
The results of this report provide evidence that insulin-like growth factor-1 binding proteins (IGFBPs) in human sera are differentially regulated as a result of severe burn injury. Using the ligand binding technique, 125I-IGF-1 visualizes 5 different protein bands corresponding to those previously reported for IGFBP-1 to 4 with apparent sizes of 23-42 kd in serum samples prepared from severely burned patients and healthy individuals. The level of IGFBP-3 was significantly decreased within 3-5 days of injury and remained depressed for up to 20 days post injury. The average level of this binding protein reached its lowest value within 3-5 days of the injury (3.8 +/- 1.48% relative to day 0-1 value, n = 4, p < 0.01). Serum samples from 3 of 4 patients showed no recovery within 20 days post injury and the level of IGFBP-3 remained significantly depressed (p < 0.01). In contrast, the levels of IGFBP-2 and IGFBP-4 increased 2 and 3 fold in the same serum samples within 3-5 days of the burn injury, respectively. This increase returns to normal (day 0-1 value) within 7-10 days for IGFBP-2, but the level of IGFBP-4 remained elevated 4 fold relative to the day 0-1 (p < 0.01). However, the abundance of IGFBP-1 in these serum samples was not significantly altered by the burn injury. By controlling for protein loading, these apparent alterations of IGFBPs in the sera of burned patients were not due to hemodilution. Similarly, significant reductions in IGFBP-3 were not likely due to IGFBP-3 specific protease activity in the sera of burn patients since incubation of sera from burn patients and normal individuals at 37 degrees C did not alter the pattern of IGFBPs in sera obtained from normal individuals. Of interest, the level of IGF-1 protein in these samples was also markedly reduced following severe burn injury similar to IGFBP-3. The results of this study suggest that a marked reduction of serum IGF-1 seen in burn patients is associated with a significant reduction of IGFBP-3, a major IGF-1 binding protein in human serum.
本报告结果表明，严重烧伤会导致人血清中胰岛素样生长因子-1结合蛋白（IGFBPs）受到不同程度的调节。采用配体结合技术，125I-IGF-1可在严重烧伤患者和健康个体的血清样本中显示出5条不同的蛋白带，对应于先前报道的IGFBP-1至4，其表观大小为23 - 42 kd。IGFBP-3水平在受伤后3 - 5天显著降低，并在受伤后长达20天内持续处于较低水平。该结合蛋白的平均水平在受伤后3 - 5天达到最低值（相对于第0 - 1天的值为3.8 +/- 1.48%，n = 4，p < 0.01）。4例患者中有3例的血清样本在受伤后20天内未恢复，IGFBP-3水平仍显著降低（p < 0.01）。相比之下，在烧伤后3 - 5天内，同一血清样本中IGFBP-2和IGFBP-4的水平分别增加了2倍和3倍。IGFBP-2的这种增加在7 - 10天内恢复正常（第0 - 1天的值），但IGFBP-4的水平相对于第0 - 1天仍升高4倍（p < 0.01）。然而，这些血清样本中IGFBP-1的丰度并未因烧伤而发生显著改变。通过控制蛋白上样量，烧伤患者血清中IGFBPs的这些明显变化并非由于血液稀释。同样，IGFBP-3的显著降低不太可能是由于烧伤患者血清中的IGFBP-3特异性蛋白酶活性，因为将烧伤患者和正常个体的血清在37℃孵育并未改变正常个体血清中IGFBPs的模式。有趣的是，与IGFBP-3类似，严重烧伤后这些样本中IGF-1蛋白的水平也显著降低。本研究结果表明，烧伤患者血清中IGF-1的显著降低与IGFBP-3（人血清中主要的IGF-1结合蛋白）的显著降低有关。
