抗血小板药物对内毒素致敏大鼠肺血流动力学对fMLP反应的影响。

Effects of antiplatelet agents on pulmonary haemodynamic response to fMLP in endotoxin primed rats.

作者信息

Song C, Suzuki S, Kubo H, Chida M, Hoshikawa Y, Tabata T, Kondo T

机构信息

Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai, Japan 980-8575.

出版信息

Thorax. 2004 Jan;59(1):39-44. doi: 10.1136/thx.2003.002022.

DOI:10.1136/thx.2003.002022

PMID:14694246

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1758845/

Abstract

BACKGROUND

The interaction between neutrophils and platelets may be important in the modulation of pulmonary haemodynamics under systemic inflammatory conditions. A study was undertaken to examine whether antiplatelet agents inhibit platelet-neutrophil adherence and ameliorate the pulmonary haemodynamic response to fMLP by inhibiting thromboxane release in endotoxin primed lungs. fMLP stimulates neutrophils but not platelets; however, thromboxane synthesis in neutrophils is very low.

METHODS

Rats were pretreated with either cilostazol (300 mg/kg) or aspirin (50 mg/kg) before endotoxin priming (5 mg/kg). Platelets in the lung were identified by fluorescent immunohistochemistry. Platelet-neutrophil adherence was analysed by flow cytometry of the lung vascular flush. The effect of fMLP (10(-6) M) on thromboxane release, lung weight (an indicator of pulmonary vasoconstriction), and lung filtration coefficient was determined in an isolated lung system perfused at a constant pressure difference.

RESULTS

Endotoxin induced platelet accumulation and platelet-neutrophil adherence in the lung capillary were completely inhibited by cilostazol and aspirin while neutrophil recruitment was not affected. The fMLP challenge caused a significant increase in thromboxane B2 levels in endotoxin primed lungs. The fMLP induced decrease in lung weight was enhanced by endotoxin priming (from -4.9 to -63.9 mg, 95% CI of mean difference -99.5 to -10.5 mg, p<0.05). The fMLP induced increase in the lung filtration coefficient was also enhanced by endotoxin priming (from 0.63 to 2.40 mg/min/cm H2O/g, 95% CI of mean difference 1.17 to 2.37 mg/min/cm H2O/g, p<0.05). Treatment with cilostazol and aspirin completely inhibited the enhanced pulmonary haemodynamic response to fMLP.

CONCLUSION

The neutrophil-platelet interaction is of critical importance in the modulation of pulmonary haemodynamics via thromboxane.

摘要

背景

在全身炎症状态下，中性粒细胞与血小板之间的相互作用可能在肺血流动力学调节中起重要作用。本研究旨在探讨抗血小板药物是否通过抑制内毒素预处理肺组织中血栓素的释放，来抑制血小板 - 中性粒细胞黏附并改善对fMLP的肺血流动力学反应。fMLP刺激中性粒细胞而非血小板；然而，中性粒细胞中的血栓素合成非常低。

方法

在内毒素预处理（5mg/kg）前，大鼠分别用西洛他唑（300mg/kg）或阿司匹林（50mg/kg）进行预处理。通过荧光免疫组织化学鉴定肺组织中的血小板。通过肺血管冲洗液的流式细胞术分析血小板 - 中性粒细胞黏附情况。在恒压差灌注的离体肺系统中，测定fMLP（10⁻⁶M）对血栓素释放、肺重量（肺血管收缩的指标）和肺滤过系数的影响。

结果

西洛他唑和阿司匹林完全抑制了内毒素诱导的肺毛细血管中血小板聚集和血小板 - 中性粒细胞黏附，而中性粒细胞募集未受影响。fMLP刺激导致内毒素预处理肺组织中血栓素B2水平显著升高。内毒素预处理增强了fMLP诱导的肺重量下降（从 -4.9降至 -63.9mg，平均差异的95%置信区间为 -99.5至 -10.5mg，p<0.05）。内毒素预处理也增强了fMLP诱导的肺滤过系数升高（从0.63升至2.40mg/min/cm H₂O/g，平均差异的95%置信区间为1.17至2.37mg/min/cm H₂O/g，p<0.05）。西洛他唑和阿司匹林治疗完全抑制了对fMLP增强的肺血流动力学反应。