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首页> 外文期刊>Toxicology and Applied Pharmacology >Tissue factor pathway inhibitor prevents airway obstruction, respiratory failure and death due to sulfur mustard analog inhalation
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Tissue factor pathway inhibitor prevents airway obstruction, respiratory failure and death due to sulfur mustard analog inhalation

机译：组织因子途径抑制剂可防止因吸入硫芥子气而引起的气道阻塞，呼吸衰竭和死亡

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Sulfur mustard (SM) inhalation causes airway injury, with enhanced vascular permeability, coagulation, and airway obstruction. The objective of this study was to determine whether recombinant tissue factor pathway inhibitor (TFPI) could inhibit this pathogenic sequence. Methods: Rats were exposed to the SM analog 2-chloroethyl ethyl sulfide (CEES) via nose-only aerosol inhalation. One hour later, TFPI (1.5mg/kg) in vehicle, or vehicle alone, was instilled into the trachea. Arterial O2 saturation was monitored using pulse oximetry. Twelve hours after exposure, animals were euthanized and bronchoalveolar lavage fluid (BALF) and plasma were analyzed for prothrombin, thrombin-antithrombin complex (TAT), active plasminogen activator inhibitor-1 (PAI-1) levels, and fluid fibrinolytic capacity. Lung steady-state PAI-1 mRNA was measured by RT-PCR analysis. Airway-capillary leak was estimated by BALF protein and IgM, and by pleural fluid measurement. In additional animals, airway cast formation was assessed by microdissection and immunohistochemical detection of airway fibrin. Results: Airway obstruction in the form of fibrin-containing casts was evident in central conducting airways of rats receiving CEES. TFPI decreased cast formation, and limited severe hypoxemia. Findings of reduced prothrombin consumption, and lower TAT complexes in BALF, demonstrated that TFPI acted to limit thrombin activation in airways. TFPI, however, did not appreciably affect CEES-induced airway protein leak, PAI-1 mRNA induction, or inhibition of the fibrinolytic activity present in airway surface liquid. Conclusions: Intratracheal administration of TFPI limits airway obstruction, improves gas exchange, and prevents mortality in rats with sulfur mustard-analog-induced acute lung injury.
机译：吸入芥末（SM）会导致气道损伤，并增加血管通透性，凝血和气道阻塞。这项研究的目的是确定重组组织因子途径抑制剂（TFPI）是否可以抑制这种致病序列。方法：通过仅鼻喷雾吸入将大鼠暴露于SM类似物2-氯乙基乙基硫化物（CEES）。一小时后，将溶媒或单独溶媒中的TFPI（1.5mg / kg）滴入气管。使用脉搏血氧仪监测动脉血氧饱和度。暴露后十二小时，对动物实施安乐死，并对支气管肺泡灌洗液（BALF）和血浆进行凝血酶原，凝血酶-抗凝血酶复合物（TAT），活性纤溶酶原激活物抑制剂1（PAI-1）水平和液体纤溶能力的分析。通过RT-PCR分析测量肺稳态PAI-1 mRNA。通过BALF蛋白和IgM以及胸腔积液评估气道毛细血管渗漏。在另外的动物中，通过显微切割和气道纤维蛋白的免疫组织化学检测来评估气道铸型的形成。结果：在接受CEES的大鼠的中枢导气道中，以含纤维蛋白的铸片形式的气道阻塞很明显。 TFPI减少了管型的形成，并限制了严重的低氧血症。在BALF中减少凝血酶原消耗和降低TAT复合物的发现表明，TFPI可以限制呼吸道中凝血酶的活化。但是，TFPI不会明显影响CEES诱导的气道蛋白泄漏，PAI-1 mRNA的诱导或气道表面液中纤溶活性的抑制。结论：气管内给予TFPI可以限制气道阻塞，改善气体交换并防止硫芥子素类似物诱发的急性肺损伤大鼠的死亡。

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