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雾化纤维蛋白溶解剂可改善直接和间接性急性肺损伤大鼠模型中的肺纤维蛋白溶解，但不能改善炎症。

Nebulized fibrinolytic agents improve pulmonary fibrinolysis but not inflammation in rat models of direct and indirect acute lung injury.

机构信息

Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.

出版信息

PLoS One. 2013;8(2):e55262. doi: 10.1371/journal.pone.0055262. Epub 2013 Feb 7.

DOI:10.1371/journal.pone.0055262
PMID:23408962
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3567078/
Abstract

BACKGROUND

Critically ill patients frequently develop acute lung injury (ALI). Disturbed alveolar fibrin turnover, a characteristic feature of ALI, is the result of both activation of coagulation and inhibition of fibrinolysis. Nebulized fibrinolytic agents could exert lung-protective effects, via promotion of fibrinolysis as well as anti-inflammation.

METHODS

Rats were challenged intratracheally with Pseudomonas aeruginosa, resulting in pneumonia as a model for direct ALI, or received an intravenous bolus infusion of lipopolysaccharide, as a model for indirect ALI. Rats were randomized to nebulization of normal saline (placebo), recombinant tissue plasminogen activator (rtPA), or monoclonal antibodies against plasminogen activator inhibitor-type 1 (anti-PAI-1).

RESULTS

Nebulized rtPA or anti-PA1-1 enhanced the bronchoalveolar fibrinolytic system, as reflected by a significant reduction of PAI-1 activity levels in bronchoalveolar lavage fluid, and a consequent increase in plasminogen activator activity (PAA) levels to supranormal values. Both treatments also significantly affected systemic fibrinolysis as reflected by a significant increase in PAA levels in plasma to supranormal levels. Neither nebulized rtPA nor anti-PA1-1 affected pulmonary inflammation. Neither treatment affected bacterial clearance of P. aeruginosa from the lungs in case of pneumonia.

CONCLUSIONS

Local treatment with rtPA or anti-PA1-1 affects pulmonary fibrinolysis but not inflammation in models of direct or indirect ALI in rats.

摘要

背景

危重症患者常发生急性肺损伤（ALI）。肺泡纤维蛋白转化紊乱是 ALI 的一个特征，这是凝血激活和纤溶抑制共同作用的结果。雾化纤维蛋白溶解剂可通过促进纤溶和抗炎发挥肺保护作用。

方法

通过气管内滴注铜绿假单胞菌建立肺炎直接 ALI 模型，或静脉推注脂多糖建立间接 ALI 模型，对大鼠进行处理。大鼠随机接受生理盐水（安慰剂）、重组组织型纤溶酶原激活剂（rtPA）或纤溶酶原激活物抑制剂-1 单克隆抗体（抗-PAI-1）雾化治疗。

结果

雾化 rtPA 或抗-PAI-1 增强了支气管肺泡内的纤维蛋白溶解系统，表现为支气管肺泡灌洗液中 PAI-1 活性水平显著降低，纤溶酶原激活物活性（PAA）水平升高至超正常值。两种治疗方法均显著影响全身纤溶，表现为血浆中 PAA 水平升高至超正常值。雾化 rtPA 或抗-PAI-1 均不影响肺部炎症。在肺炎模型中，两种治疗方法均不影响 P. aeruginosa 从肺部的清除。

结论

局部应用 rtPA 或抗-PAI-1 可影响大鼠直接或间接 ALI 模型中的肺纤维蛋白溶解，但不影响炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55d7/3567078/58c8e93af326/pone.0055262.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55d7/3567078/d532fe6ac720/pone.0055262.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55d7/3567078/cc7bcc125e2a/pone.0055262.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55d7/3567078/72a99c13ed78/pone.0055262.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55d7/3567078/ca2282ac1c1e/pone.0055262.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55d7/3567078/786d1afe6669/pone.0055262.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55d7/3567078/ee3b076eafa5/pone.0055262.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55d7/3567078/58c8e93af326/pone.0055262.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55d7/3567078/d532fe6ac720/pone.0055262.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55d7/3567078/cc7bcc125e2a/pone.0055262.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55d7/3567078/72a99c13ed78/pone.0055262.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55d7/3567078/ca2282ac1c1e/pone.0055262.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55d7/3567078/786d1afe6669/pone.0055262.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55d7/3567078/ee3b076eafa5/pone.0055262.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55d7/3567078/58c8e93af326/pone.0055262.g007.jpg

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2
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3
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