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脂质体包裹的血红蛋白不会加重内毒素诱导的肺损伤。

Liposome-encapsulated hemoglobin does not exacerbate endotoxin-induced lung injury.

作者信息

Rabinovici R, Spirig A, Abdullah F, Phillip D R, Ovadia P, Rudolph A

机构信息

Section of Trauma & Surgical Critical Care, Yale University School of Medicine, New Haven, CT, USA.

出版信息

Crit Care Med. 2000 Jun;28(6):1924-30. doi: 10.1097/00003246-200006000-00040.

Abstract

OBJECTIVE

To test the hypothesis that liposome encapsulated hemoglobin (LEH), an experimental oxygen-carrying fluid, exacerbates endotoxin-induced lung injury in the rat.

DESIGN

Prospective, randomized animal study.

SETTING

University animal laboratory.

METHODS

Anesthetized Sprague-Dawley rats (n = 8-13) were infused with LEH (10% of estimated total blood volume) or vehicle (0.9% NaCl). Thirty minutes later, Escherichia coli endotoxin (3.6 mg/kg, i.v.) or vehicle (0.9% NaCl) was administered, and skeletal muscle oxygen tension as well as lung injury were assessed at 2, 4, and 8 hrs. Oxygen tension was measured using a miniaturized thin film oxygen sensor placed in the rectus abdominis muscle, and lung injury was evaluated by determining lung weights, lung myeloperoxidase activity, lung tissue tumor necrosis factor-alpha level, and protein concentration in bronchoalveolar lavage fluid.

RESULTS

The intravenous bolus injection of E. coli endotoxin elevated lung water content (33% +/- 5%; p < .01 vs. sham controls), myeloperoxidase activity (56% +/- 6%; p < .01), and tumor necrosis factor-alpha production (1320 +/- 154 pg/g lung tissue; p < .05 vs. undetected levels in sham controls), as well as induced protein accumulation in bronchoalveolar lavage fluid (258% +/- 38%; p < .01) and skeletal muscle hypoxia (52 +/- 8 mm Hg; p < .05). Pretreatment with LEH, which when infused alone did not induce lung injury, had no effect on these responses.

CONCLUSION

In this specific model of endotoxin-induced lung injury, LEH does not exacerbate microvascular leakage and leukosequestration, the hallmarks of adult respiratory distress syndrome.

摘要

目的

验证脂质体包裹血红蛋白(LEH)这一实验性携氧液体是否会加重大鼠内毒素诱导的肺损伤这一假说。

设计

前瞻性随机动物研究。

地点

大学动物实验室。

方法

对麻醉的斯普拉格-道利大鼠(n = 8 - 13)输注LEH(估计全血容量的10%)或赋形剂(0.9%氯化钠)。30分钟后,给予大肠杆菌内毒素(3.6毫克/千克,静脉注射)或赋形剂(0.9%氯化钠),并在2、4和8小时评估骨骼肌氧张力以及肺损伤情况。使用置于腹直肌的小型化薄膜氧传感器测量氧张力,并通过测定肺重量、肺髓过氧化物酶活性、肺组织肿瘤坏死因子-α水平以及支气管肺泡灌洗液中的蛋白质浓度来评估肺损伤。

结果

静脉推注大肠杆菌内毒素可使肺含水量升高(33% ± 5%;与假手术对照组相比,p < .01)、髓过氧化物酶活性升高(56% ± 6%;p < .01)、肿瘤坏死因子-α生成增加(1320 ± 154皮克/克肺组织;与假手术对照组未检测到的水平相比,p < .05),还可导致支气管肺泡灌洗液中蛋白质积聚(258% ± 38%;p < .01)以及骨骼肌缺氧(52 ± 8毫米汞柱;p < .05)。单独输注时不会诱导肺损伤的LEH预处理对这些反应没有影响。

结论

在这个内毒素诱导的肺损伤特定模型中,LEH不会加重微血管渗漏和白细胞扣押,而这两者是成人呼吸窘迫综合征的特征。

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