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红细胞氧化还原硫醇状态对血液流变学参数的调节作用。

Modulation of hemorheological parameters by the erythrocyte redox thiol status.

作者信息

Almeida José Pedro, Carvalho Filomena Almeida, Freitas Teresa, Saldanha Carlota

机构信息

University of Lisbon Medical School, Santa Maria Hospital, 1649-028 Lisbon, Portugal.

出版信息

Clin Hemorheol Microcirc. 2008;40(2):99-111.

Abstract

BACKGROUND

There is growing knowledge about the association between hemorheological blood disorders and compromised microcirculation in erythrocyte abnormalities. Effects of the non-neuronal cholinergic elements, especially acetylcholinesterase, on the erythrocyte hemorheological parameters were characterized in the past. However, alterations of these parameters have not been studied under the influence of the cellular redox thiol status.

METHODS

Aliquots of venous blood from ten healthy male subjects were incubated in vitro with increasing concentrations of a thiol reducer agent (dithiothreitol 1, 10, 50 microM final concentrations) in the presence and absence of acetylcholinesterase substrate (acetylcholine) or inhibitor (velnacrine maleate). The following parameters were determined in all blood samples aliquots: erythrocyte aggregation, erythrocyte deformability and lipid membrane fluidity. Blood smears were performed.

RESULTS

Dithiothreitol induces no significant changes on the hemorheological behaviour of human red cells. Upon intracellular thiol stimulation, the presence of AChE effectors (either acetylcholine or velnacrine) decreases erythrocyte aggregation and elongation indexes.

CONCLUSION

The addition of DTT to blood samples aliquots, contributing to the redox thiol status, is not directly involved in the modulation of erythrocyte rheological properties. However, upon acetylcholinesterase modulation by its substrate or inhibitor, changes on the hemorheological parameters are triggered by DTT. Associated pharmacological interest is considerable to address the hemorheology-hemostasis-microcirculation triad disorders.

摘要

背景

关于血液流变学紊乱与红细胞异常中微循环受损之间的关联,人们的认识日益增加。过去已对非神经元胆碱能成分,尤其是乙酰胆碱酯酶对红细胞血液流变学参数的影响进行了表征。然而,尚未研究这些参数在细胞氧化还原硫醇状态影响下的变化。

方法

将来自10名健康男性受试者的静脉血 aliquots 在体外与浓度递增的硫醇还原剂(二硫苏糖醇,终浓度为1、10、50微摩尔)一起孵育,同时存在和不存在乙酰胆碱酯酶底物(乙酰胆碱)或抑制剂(马来酸韦那克林)。在所有血液样本 aliquots 中测定以下参数:红细胞聚集、红细胞变形性和脂质膜流动性。进行血涂片检查。

结果

二硫苏糖醇对人红细胞的血液流变学行为无显著影响。在细胞内硫醇刺激后,AChE 效应物(乙酰胆碱或韦那克林)的存在会降低红细胞聚集和伸长指数。

结论

向血液样本 aliquots 中添加 DTT 以改变氧化还原硫醇状态,并不直接参与红细胞流变学特性的调节。然而,在乙酰胆碱酯酶被其底物或抑制剂调节后,DTT 会引发血液流变学参数的变化。解决血液流变学 - 止血 - 微循环三联症的相关药理学意义重大。

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