Hendriks H F, Horan M A, Durham S K, Earnest D L, Brouwer A, Hollander C F, Knook D L
TNO Institute for Experimental Gerontology, Rijswijk, The Netherlands.
Mech Ageing Dev. 1987 Dec;41(3):241-50. doi: 10.1016/0047-6374(87)90044-3.
The plasma disappearance of endotoxin and endotoxin-induced hepatic injury were studied in two rat models: the aging rat and the subacutely hypervitaminotic A rat. The choice of these models was based on their respective association with a decreased or increased Kupffer cell endocytic activity. The half-life of endotoxin (E. coli O26: B6, phenol extracted) in plasma was significantly prolonged in aged rats as measured by both the Limulus assay (t1/2 = 2.1 +/- 0.1 h in 3-6-month-old, and 3.3 +/- 0.3 h in 24-36-month-old rats) and 51Cr-labeled endotoxin radioactivity assay (t1/2 = 5.3 +/- 0.3 h in 3-6-month old and 7.7 +/- 0.6 h in 24 36-month-old rats). In subacute hypervitaminosis A, the half-life of endotoxin was significantly decreased in the Limulus assay (t1/2 = 2.1 +/- 0.1 h in 3-6-month old and 1.4 +/- 0.2 h in subacutely hypervitaminotic A rats), but not in the radioactivity assay (t1/2 = 5.3 +/- 0.3 h in 3-6-month-old and 5.0 +/- 0.4 h in subacutely hypervitaminotic A rats). Hundred percent mortality was observed at a dose of 2 mg endotoxin/100 g body wt. in old rats, but not in young rats. Only 1 of 7 young subacutely hypervitaminotic A rats died following injection of this dose of endotoxin. The dose of endotoxin which caused only minimal parenchymal liver cell injury in young rats induced substantial parenchymal cell injury in old rats and subacutely hypervitaminotic A rats as determined by both histological and biochemical parameters. It is concluded that some basic characteristics of experimental animals, such as age and nutritional status, can dramatically influence the sensitivity to endotoxin and this is not necessarily correlated with the rate of endotoxin clearance.
在内毒素血症大鼠模型（老龄大鼠）和亚急性维生素A过多症大鼠模型中，研究了内毒素的血浆清除情况以及内毒素诱导的肝损伤。选择这两种模型是基于它们分别与枯否细胞内吞活性降低或升高有关。通过鲎试剂法（3 - 6月龄大鼠的t1/2 = 2. /- 0.1小时，24 - 36月龄大鼠的t1/2 = 3.3 /- 0.3小时）和51Cr标记的内毒素放射性测定法（3 - 6月龄大鼠的t1/2 = 5.3 /- 0.3小时，24 - 36月龄大鼠的t1/2 = 7.7 /- 0.6小时）测定，老龄大鼠血浆中内毒素（大肠杆菌O26:B6，酚提取）的半衰期显著延长。在亚急性维生素A过多症模型中，鲎试剂法测定内毒素的半衰期显著缩短（3 - 6月龄大鼠的t1/2 = 2.1 /- 0.1小时，亚急性维生素A过多症大鼠的t1/2 = 1.4 /- 0.2小时），但放射性测定法结果未显示缩短（3 - 6月龄大鼠的t1/2 = 5.3 /- 0.3小时，亚急性维生素A过多症大鼠的t1/2 = 5.0 /- 0.4小时）。给予2mg内毒素/100g体重剂量时，老龄大鼠出现100%死亡，而年轻大鼠未出现死亡。7只亚急性维生素A过多症年轻大鼠中，仅1只在注射该剂量内毒素后死亡。通过组织学和生化参数测定发现，在年轻大鼠中仅引起最小程度实质肝细胞损伤的内毒素剂量，在老龄大鼠和亚急性维生素A过多症大鼠中却诱导了实质性的实质细胞损伤。由此得出结论，实验动物的一些基本特征，如年龄和营养状况，可显著影响对内毒素的敏感性，且这不一定与内毒素清除率相关。
