Wojnar M M, Fan J, Li Y H, Lang C H
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Pennsylvania State College of Medicine, Hershey, Pennsylvania 17033, USA.
Am J Physiol. 1999 Mar;276(3):E455-64. doi: 10.1152/ajpendo.1999.276.3.E455.
The purpose of the present study was to determine whether acute changes in the insulin-like growth factor (IGF) system induced by mild surgical trauma/fasting or endotoxin [lipopolysaccharide (LPS)] are differentially modulated by total enteral nutrition (TEN) or total parenteral nutrition (TPN). Rats had vascular catheters and a gastrostomy tube surgically placed and were fasted overnight. The next morning animals randomly received an isocaloric, isonitrogenous (250 kcal. kg-1. day-1, 1.6 g N. kg-1. day-1) infusion of either TEN or TPN for 48 h. Then rats were injected intravenously with Escherichia coli LPS (1 mg/kg) while nutritional support was continued. Time-matched control animals were injected with saline. After mild surgical trauma and an 18-h fast, TEN was more effective at increasing plasma IGF-I levels than TPN. Subsequent injection of LPS decreased IGF-I in blood, liver, and muscle in both TEN- and TPN-fed rats compared with saline-injected control animals. However, this decrease was approximately 30% greater in rats fed TPN compared with those fed TEN. LPS-induced downregulation of IGF-I mRNA expression in liver and muscle was also more prominent in TPN-fed rats. The LPS-induced increase in plasma corticosterone and tumor necrosis factor-alpha was greater (2- and 1.6-fold, respectively) in TPN-fed rats, and these changes were consistent with the greater reduction in IGF-I seen in these animals. In similarly treated rats allowed to survive for 24 h after LPS injection, the LPS-induced increase in the urinary 3-methylhistidine-to-creatinine ratio was smaller in TEN-fed rats. In summary, LPS reduced systemic levels of IGF-I as well as IGF-I protein and mRNA in critical target organs. Enteral feeding greatly attenuated this response. Maintenance of higher IGF-I levels in TEN-fed rats was associated with a reduction in inflammatory cytokine levels and lower rates of myofibrillar degradation.
本研究的目的是确定轻度手术创伤/禁食或内毒素[脂多糖（LPS）]诱导的胰岛素样生长因子（IGF）系统的急性变化是否受到全肠内营养（TEN）或全肠外营养（TPN）的不同调节。大鼠通过手术放置血管导管和胃造瘘管，并禁食过夜。第二天早上，动物随机接受等热量、等氮量（250千卡·千克-1·天-1，1.6克氮·千克-1·天-1）的TEN或TPN输注，持续48小时。然后在继续营养支持的同时，给大鼠静脉注射大肠杆菌LPS（1毫克/千克）。时间匹配的对照动物注射生理盐水。在轻度手术创伤和禁食18小时后，TEN在提高血浆IGF-I水平方面比TPN更有效。与注射生理盐水的对照动物相比，随后注射LPS使TEN喂养和TPN喂养的大鼠血液、肝脏和肌肉中的IGF-I降低。然而，TPN喂养的大鼠的这种降低比TEN喂养的大鼠大约高30%。LPS诱导的肝脏和肌肉中IGF-I mRNA表达的下调在TPN喂养的大鼠中也更明显。LPS诱导的血浆皮质酮和肿瘤坏死因子-α的增加在TPN喂养大鼠中更大（分别为2倍和1.6倍），这些变化与这些动物中IGF-I的更大降低一致。在LPS注射后存活24小时的类似处理大鼠中，LPS诱导的尿3-甲基组氨酸与肌酐比值的增加在TEN喂养的大鼠中较小。总之，LPS降低了全身IGF-I水平以及关键靶器官中的IGF-I蛋白和mRNA。肠内喂养大大减弱了这种反应。TEN喂养的大鼠中较高IGF-I水平的维持与炎症细胞因子水平的降低和肌原纤维降解率的降低有关。
