Rivera C A, Tcharmtchi M H, Mendoza L, Smith C W
Baylor College of Medicine, Section of Leukocyte Biology, 1100 Bates, Rm. 6014, Houston, TX 77030, USA.
J Appl Physiol (1985). 2003 Oct;95(4):1656-63. doi: 10.1152/japplphysiol.00302.2003. Epub 2003 Jun 6.
Hindlimb unloading (HU) is known to induce physiological alterations in various organ systems that mimic some responses observed after exposure to microgravity. In the present study, the effects of up to 4 wk of HU on the liver were assessed in male Wistar rats and two mouse strains: endotoxin-sensitive C57BL/6 mice and endotoxin-resistant C3H/HEJ mice. Plasma levels of endotoxin, a known stimulator of hepatic injury, were measured in portal and systemic blood samples. Endotoxin was elevated by approximately 50% in portal blood samples of mice and rats but was not detectable in systemic blood. This low-grade portal endotoxemia was associated with hepatic injury in rats and C57BL/6 mice as indicated by inflammation and elevated serum transaminase activities. Blood levels of the cytokine TNF-alpha were increased by approximately 50% in C57BL/6 mice; no significant elevation of this cytokine was detected in rats. Messenger RNA levels of the acute-phase proteins serum amyloid A, haptoglobin, and lipopolysaccharide binding protein were significantly enhanced after 3 wk of HU in endotoxin-sensitive rodents. In contrast, no histological changes or significant increases in serum enzyme activity were detected after HU in C3H/HEJ mice despite portal endotoxin levels of 222 +/- 83.4 pg/ml. At the 3-wk time point, expression of acute-phase proteins was not elevated in C3H/HEJ mice; however, expression after 4 wk of HU was similar to endotoxin-sensitive rodents. In conclusion, these findings indicate that HU induced mild portal endotoxemia, which contributed to the observed hepatic injury in endotoxin-sensitive rodents.
后肢卸载（HU）已知会在各种器官系统中引发生理变化，这些变化模拟了暴露于微重力后观察到的一些反应。在本研究中，在雄性Wistar大鼠以及两种小鼠品系（内毒素敏感的C57BL/6小鼠和内毒素耐受的C3H/HEJ小鼠）中评估了长达4周的HU对肝脏的影响。在门静脉和全身血液样本中测量了已知的肝损伤刺激物内毒素的血浆水平。小鼠和大鼠门静脉血样本中的内毒素升高了约50%，但在全身血液中未检测到。这种低度门静脉内毒素血症与大鼠和C57BL/6小鼠的肝损伤有关，炎症和血清转氨酶活性升高表明了这一点。C57BL/6小鼠中细胞因子TNF-α的血液水平升高了约50%；在大鼠中未检测到该细胞因子的显著升高。在对内毒素敏感的啮齿动物中，HU 3周后急性期蛋白血清淀粉样蛋白A、触珠蛋白和脂多糖结合蛋白的信使核糖核酸水平显著增强。相比之下，尽管C3H/HEJ小鼠的门静脉内毒素水平为222±83.4 pg/ml，但HU后未检测到组织学变化或血清酶活性的显著增加。在3周时间点，C3H/HEJ小鼠中急性期蛋白的表达未升高；然而，HU 4周后的表达与对内毒素敏感的啮齿动物相似。总之，这些发现表明HU诱导了轻度门静脉内毒素血症，这导致了对内毒素敏感的啮齿动物中观察到的肝损伤。
