Dickerson R N, Manzo C B, Charland S L, Settle R G, Stein T P, Kuhl D A, Rajter J J
University of Tennessee, Memphis.
J Surg Res. 1995 Mar;58(3):260-6. doi: 10.1006/jsre.1995.1041.
To determine the influence of insulin-like growth factor-1 (IGF-1) on nitrogen loss and hepatic response to critical illness, 34 male Sprague-Dawley rats (190-230 g) were randomized to receive parenteral nutrition (PN) only (Ctrl), PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide at 6 mg/kg/day (LPS), or PN plus LPS plus rhIGF-1 (IGF-1) at 3 mg/kg/day for 48 hr. Prior to randomization, all animals underwent iv cannulation and 30 hr of adaptation to PN. All animals received isocaloric and isonitrogenous PN (glucose 170 kcal/kg/day and nitrogen 1.1 g/kg/day) and were kept NPO except for water ad libitum. [15N]glycine was infused in all animals for determination of liver fractional synthetic rate. Cumulative nitrogen balance during endotoxemia was significantly different from each other (+72 +/- 42, -217 +/- 131, -114 +/- 137 mg/kg/48 hr for the Ctrl, LPS, and IGF-1 groups, respectively; ANOVA, P < 0.001). Endotoxin significantly increased the urinary 3-methylhistidine/creatinine ratio (0.24 +/- 0.05, 0.55 +/- 0.12, 0.48 +/- 0.17 for the Ctrl, LPS, and IGF-1 groups, respectively; ANOVA, P < 0.001); however, IGF-1 did not significantly reduce the ratio. Endotoxin induced a significant increase in liver fractional synthetic rate (29 +/- 8, 56 +/- 18, 64 +/- 12%/day for the Ctrl, LPS, and IGF-1 groups, respectively; ANOVA, P < 0.01) and depressed hepatic cytochrome P450 concentration (0.54 +/- 0.19, 0.22 +/- 0.07, 0.19 +/- 0.07 nmol/mg protein, respectively; ANOVA, P < 0.05) and ethoxycoumarin O-deethylase (ECOD) activity (103 +/- 73, 29 +/- 13, 17 +/- 11, pmol/mg/min, respectively; ANOVA, P < 0.01); however, rhIGF-1 did not significantly alter these hepatic variables during endotoxin infusion. Recombinant human insulin-like growth factor-1 significantly improved nitrogen balance without compromising hepatic response as measured by liver fractional synthetic rate, cytochrome P450 concentration, and ECOD activity in endotoxemic parenterally fed rats.
为确定胰岛素样生长因子-1（IGF-1）对氮损失及肝脏对危重病反应的影响，将34只雄性Sprague-Dawley大鼠（190 - 230克）随机分为三组，分别仅接受肠外营养（PN）（对照组）、PN加每天以6毫克/千克持续输注大肠杆菌026:B6脂多糖（LPS），或PN加LPS加每天3毫克/千克的重组人胰岛素样生长因子-1（rhIGF-1）（IGF-1组），持续48小时。在随机分组前，所有动物均进行静脉插管并对PN适应30小时。所有动物均接受等热量和等氮量的PN（葡萄糖170千卡/千克/天，氮1.1克/千克/天），除自由饮水外均禁食。向所有动物输注[15N]甘氨酸以测定肝脏的分数合成率。内毒素血症期间的累积氮平衡在各组间差异显著（对照组、LPS组和IGF-1组分别为+72±42、-217±131、-114±137毫克/千克/48小时；方差分析，P<0.001）。内毒素显著增加尿中3 - 甲基组氨酸/肌酐比值（对照组、LPS组和IGF-1组分别为0.24±0.05、0.55±0.12、0.48±0.17；方差分析，P<0.001）；然而，IGF-1并未显著降低该比值。内毒素导致肝脏分数合成率显著增加（对照组、LPS组和IGF-1组分别为29±8、56±18、64±12%/天；方差分析，P<0.01），并降低肝脏细胞色素P450浓度（分别为0.54±0.19、0.22±0.07、0.19±0.07纳摩尔/毫克蛋白；方差分析，P<0.05）和乙氧香豆素O - 脱乙基酶（ECOD）活性（分别为103±73、29±13、17±11皮摩尔/毫克/分钟；方差分析，P<0.01）；然而，在输注内毒素期间，rhIGF-1并未显著改变这些肝脏变量。在内毒素血症的肠外营养喂养大鼠中，重组人胰岛素样生长因子-1显著改善了氮平衡，且未影响以肝脏分数合成率、细胞色素P450浓度和ECOD活性衡量的肝脏反应。
