Capillary Endothelial Thrombomodulin Expression and Fibrin Deposition in Rats with Continuous and Bolus Lipopolysaccharide Administration
Capillary Endothelial Thrombomodulin Expression and Fibrin Deposition in Rats with Continuous and Bolus Lipopolysaccharide Administration
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DOI：
10.1097/01.lab.0000080606.96797.a5
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发表时间：
2003-08
影响因子：
5
通讯作者：
Y. Terada;Y. Eguchi;S. Nosaka;T. Toba;Tatsuo Nakamura;Y. Shimizu
中科院分区：
文献类型：
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作者：
Y. Terada;Y. Eguchi;S. Nosaka;T. Toba;Tatsuo Nakamura;Y. Shimizu
我们研究了毛细血管内皮损伤，纤维蛋白沉积和血栓调节蛋白（Tm）表达的变化，在大鼠接受连续或弹丸静脉内脂多糖（LPS）。大鼠连续静脉输注LPS（0.1，0.2，0.5或1.0 mg/kg/hr）长达6小时。其他动物静脉注射LPS（20 mg/kg），然后连续输注相同剂量的生理盐水，持续3小时。取肺、肝和肾，用化学方法检测血栓调节蛋白表达和纤维蛋白沉积。在开始连续LPS给药（1.0 mg/kg/hr）的2至4小时内，肺、肝和肾管周毛细血管中Tm表达开始剂量和时间依赖性减少，并在3小时时完全消失，尽管Tm仍保留在肾小球中。在接受连续LPS给药的大鼠中，观察到的纤维蛋白沉积量随器官、剂量和治疗持续时间而变化，但在肺中几乎没有沉积。LPS推注后，肺、肝和肾小管周围毛细血管内皮的Tm在治疗后20 ~ 40分钟降低，然后在治疗后120 ~ 180分钟恢复，但肾小球的Tm活性没有改变。在肝脏、肾小球和管周毛细血管中观察到纤维蛋白沉积，但在肺中未观察到。LPS给药引起的内皮损伤取决于LPS的剂量和治疗的持续时间。纤维蛋白沉积的量在器官之间以及内皮与内毒素之间的接触持续时间不同。
We studied capillary endothelial injury, as demonstrated by fibrin deposition and changes in thrombomodulin (Tm) expression, in rats receiving continuous or bolus iv lipopolysaccharide (LPS). Rats were continuously infused with iv LPS (0.1, 0.2, 0.5, or 1.0 mg/kg/hr) for up to 6 hours. Others were given a bolus iv dose of LPS (20 mg/kg), and then the same dose of saline as a continuous infusion was administered for up to 3 hours. Harvested lungs, livers, and kidneys were examined immunohistochemically for thrombomodulin expression and fibrin deposition. Tm expression began to diminish dose- and time-dependently in lung, liver, and renal peritubular capillaries within 2 to 4 hours of the start of continuous LPS administration (1.0 mg/kg/hr) and had completely disappeared by 3 hours, although Tm remained in the glomerulus. The amount of fibrin deposition observed varied with the organ, dose, and duration of treatment in rats that received continuous LPS administration, but little was deposited in the lung. After bolus LPS administration, Tm in the endothelia of lung, liver, and peritubular capillaries diminished 20 to 40 minutes after treatment and then recovered 120 to 180 minutes after treatment, but the Tm activity of the glomerulus did not change. Fibrin deposition in the capillaries was observed in the liver, glomerulus, and peritubular capillaries, but not in the lung. Endothelial injury by LPS administration is dependent on the dose of LPS and the duration of treatment. The amount of fibrin deposition differs among organs and with the duration of contact between the endothelium and the endotoxin.