Effects of initial passage of endotoxin through the liver on the extent of acute lung injury in a rat model

Effects of initial passage of endotoxin through the liver on the extent of acute lung injury in a rat model
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DOI:
10.1097/01.shk.0000224960.17274.6f
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发表时间:
2006-09-01
期刊:
影响因子:
3.1
通讯作者:
Ishizaka, Akitosi
Ishizaka, Akitosi
中科院分区:
医学2区
文献类型:
--
作者:
Shimada, Hisato;Hasegawa, Naoki;Ishizaka, Akitosi

文献摘要

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我们假设脂多糖(LPS)引起的急性肺损伤(ALI)的程度与其通过肝脏的初始通道有关。我们通过在1小时内通过门静脉(PV)或下腔静脉(IVC)向120只雄性Wistar大鼠给予5 mg/kg LIDS或盐水来测试这一假设。4个实验组分别向PV、IVC、PV和IVC注入生理盐水、LPS(LPS-PV组)和LIPS(LPS-IVC组)。在(51)铬-LPS输注开始后15和30 min,LPS-PV组的肝脏γ计数高于LPS-IVC组。肺组织中125碘-白蛋白计数与血浆中125碘-白蛋白计数的比值(作为肺微血管通透性的评估)在LPS刺激开始后240分钟,多形核细胞的积累(通过髓过氧化物酶活性评估)和LPS输注开始后60和240分钟肺中肿瘤坏死因子a的浓度,LPS-IVC组高于LPS-PV组。在LIDS输注开始后,观察到炎症的几个指标和LPS诱导的ALI程度的显著差异,这取决于它是通过PV还是IVC输送。这些观察结果表明,截留LPS在其最初通过肝循环可能会减弱LPS诱导的ALI在4小时内启动LPS刺激。
We hypothesized that the extent of acute lung injury (ALI) caused by lipopolysaccharide (LPS) is modified with its initial passage through the liver. We tested this hypothesis by administering LIDS, 5 mg/kg, or saline to 120 male Wistar rats via the portal vein (PV) or the inferior vena cava (IVC) over 1 h. Four experimental groups of rats were administered saline into the PV, saline into the IVC, LPS into the PV (LPS-PV group), and LIPS into the IVC (LPS-IVC group), respectively. At 15 and 30 min after onset of (51)Chromium-LPS infusion, the gamma counts in the liver were higher in the LPS-PV group than that in the LPS-IVC group. The ratio of 125 Iodine-albumin counts in lung tissue to that in plasma per unit of weight (as an assessment of pulmonary microvascular permeability) at 240 min after onset of LPS stimulation, the accumulation of polymorphonuclear cell (assessed by myeloperoxidase activity) and the concentration of tumor necrosis factor a in the lung at 60 and 240 min after onset of LPS infusion, were higher in the LPS-IVC group than in the LPS-PV group. Significant differences in several factors indicative of inflammation and in the extent of LPS-induced ALI were observed after the onset of LIDS infusion, depending on whether it was delivered via the PV or the IVC. These observations suggest that the entrapping of LPS during its initial passage through the hepatic circulation may attenuate LPS-induced ALI within 4 h of initiation of LPS stimulation.