Fan J, Molina P E, Gelato M C, Lang C H
Department of Surgery, State University of New York, Stony Brook 11794-8191.
Endocrinology. 1994 Apr;134(4):1685-92. doi: 10.1210/endo.134.4.7511091.
The purpose of the present study was to investigate the regulation of plasma and tissue levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-1, -2, and -3 (IGFBP-1, -2, and -3) in rats injected with Escherichia coli lipopolysaccharide (LPS), a component of the outer cell wall of gram-negative bacteria. When injected iv into conscious overnight fasted rats, plasma IGF-I levels were initially decreased within 1 h, maximally depressed at 4 h, and still only 35-45% of control values at 24 h. GH levels were reduced as early as 30 min after LPS, averaged 80-90% of control values between 1-4 h, but had returned to basal levels by 24 h. The magnitude and duration of these changes were similar regardless of whether 100 or 10 micrograms/100 g BW (LD20 and LD0, respectively) LPS were injected. Plasma levels of IGFBP-1 and a 28K mol wt BP (BP-28K) were elevated 2- to 3-fold 4 h after LPS treatment, whereas IGFBP-3 and -2 levels were unchanged. The elevation in plasma IGFBP-1 and IGFBP-28K was observed as early as 1 h and was sustained for up to 24 h after LPS treatment. IGF-I levels were decreased 30-50% in liver, pituitary, and skeletal muscle, unchanged in brain, and elevated 5-fold in kidney in response to LPS. Of the tissues sampled, IGFBP-3 and -2 were selectively elevated in liver after LPS treatment. IGFBP-1 was increased in liver, muscle, and kidney in response to LPS. The level of the 28,000 mol wt BP was increased in liver (83%) and not changed in muscle or brain. These data indicate that LPS produces both rapid and sustained alterations in circulating levels of GH, IGF-I, and IGFBPs. Furthermore, there were marked tissue-specific changes in levels of IGF-I and IGFBPs. LPS-induced changes in plasma and tissue IGFBP-3 were not regulated by changes in GH, and changes in insulin could not explain the alterations in IGFBP-1 and -2. These results suggest that after the injection of LPS, changes in IGF-I and IGFBP levels are regulated by a mechanism(s) different from those previously described.
本研究的目的是调查注射大肠杆菌脂多糖（LPS，革兰氏阴性菌外细胞壁的一种成分）的大鼠血浆和组织中胰岛素样生长因子-I（IGF-I）以及IGF结合蛋白-1、-2和-3（IGFBP-1、-2和-3）的调节情况。当将LPS静脉注射到过夜禁食的清醒大鼠体内时，血浆IGF-I水平最初在1小时内下降，4小时时降至最低，24小时时仍仅为对照值的35%-45%。LPS注射后最早30分钟GH水平就降低，在1-4小时之间平均为对照值的80%-90%，但到24小时时已恢复到基础水平。无论注射100微克/100克体重还是10微克/100克体重（分别为LD20和LD0）的LPS，这些变化的幅度和持续时间都相似。LPS处理4小时后，血浆IGFBP-1和一种28K分子量的结合蛋白（BP-28K）水平升高2至3倍，而IGFBP-3和-2水平未改变。LPS处理后最早1小时就观察到血浆IGFBP-1和IGFBP-28K升高，并持续至24小时。作为对LPS的反应，肝脏、垂体和骨骼肌中的IGF-I水平降低30%-50%，大脑中未改变，肾脏中升高5倍。在采样的组织中，LPS处理后肝脏中IGFBP-3和-2选择性升高。作为对LPS的反应，肝脏、肌肉和肾脏中的IGFBP-1升高。28,000分子量结合蛋白的水平在肝脏中升高（83%），在肌肉或大脑中未改变。这些数据表明，LPS会使GH、IGF-I和IGFBPs的循环水平产生快速且持续的改变。此外，IGF-I和IGFBPs的水平存在明显的组织特异性变化。LPS诱导的血浆和组织IGFBP-3变化不受GH变化的调节，胰岛素的变化也无法解释IGFBP-1和-2的改变。这些结果表明，注射LPS后，IGF-I和IGFBP水平的变化是由一种不同于先前描述的机制调节的。
