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基于血红蛋白的氧载体不会改变血小板功能:三种化学修饰血红蛋白溶液的研究

Hemoglobin-based oxygen carriers do not alter platelet functions: study of three chemically modified hemoglobin solutions.

作者信息

Toussaint Marie, Latger-Cannard Véronique, Caron Alexis, Lecompte Thomas, Vigneron Claude, Menu Patrick

机构信息

Université Henri Poincaré Nancy 1, France.

出版信息

Intensive Care Med. 2003 Jan;29(1):62-8. doi: 10.1007/s00134-002-1558-1. Epub 2002 Nov 30.

DOI:10.1007/s00134-002-1558-1
PMID:12528024
Abstract

OBJECTIVE

Chemically modified hemoglobins are being developed as potential oxygen-carrying blood substitutes (HBOCs). Clinical and preclinical data demonstrate the vasoactive properties of HBOCs by trapping of nitric oxide, which is also known to have platelet inhibitory activities properties. This study evaluated the effects of three structurally different HBOCs (Hb-Dex-BTC, alphaalpha-Hb, and o-raffinose-poly-Hb) on platelet functions in vitro to compare to those elicited by plasma substitutes, such as hydroxyethylstarch.

DESIGN

Platelet activation state was assessed using platelet-rich plasma diluted to 20% (v/v) with the different solutions, by main measuring glycoproteins (GPIb, GPIIb/IIIa, and P-selectin) using flow cytometry. Aggregation was assessed by impedance aggregometry on whole blood hemodiluted to 20% (v/v) with the solutions.

SETTING

Biological hematology department of the university hospital of Nancy-Brabois.

PATIENTS AND PARTICIPANTS

Ten healthy volunteers consent and informed of the study who denied taking any drugs at the time of the experiment.

MEASUREMENTS AND RESULTS

None of these solutions induced activation nor modified reactivity of platelets as measured by the surface expression of glycoproteins GPIb, GPIIb/IIIa, and P-selectin. Moreover, none of these solutions induced platelet aggregation when added alone, nor modified the aggregation patterns of platelets induced by collagen (0.5 microg/ml) and thrombin receptor agonist peptide (12.5 microM).

CONCLUSIONS

The three tested structurally different HBOCs, as with hydroxyethylstarch, did not alter platelet functions in vitro.

摘要

目的

化学修饰血红蛋白正被开发为潜在的携氧血液替代品(HBOCs)。临床和临床前数据表明,HBOCs具有通过捕获一氧化氮而产生的血管活性特性,而一氧化氮也具有血小板抑制活性。本研究评估了三种结构不同的HBOCs(Hb-Dex-BTC、αα-Hb和o-棉子糖-聚Hb)对体外血小板功能的影响,并与血浆替代品(如羟乙基淀粉)所引发的影响进行比较。

设计

使用用不同溶液稀释至20%(v/v)的富血小板血浆,通过流式细胞术主要检测糖蛋白(GPIb、GPIIb/IIIa和P-选择素)来评估血小板活化状态。通过用溶液将全血稀释至20%(v/v)后进行阻抗聚集法评估聚集情况。

地点

南锡-布拉博瓦大学医院生物血液学系。

患者和参与者

10名健康志愿者同意并被告知该研究,他们在实验时否认服用任何药物。

测量和结果

通过糖蛋白GPIb、GPIIb/IIIa和P-选择素的表面表达测量,这些溶液均未诱导血小板活化或改变其反应性。此外,这些溶液单独添加时均未诱导血小板聚集,也未改变由胶原蛋白(0.5微克/毫升)和凝血酶受体激动肽(12.5微摩尔)诱导的血小板聚集模式。

结论

三种经过测试的结构不同的HBOCs与羟乙基淀粉一样,在体外不会改变血小板功能。

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