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早产儿血小板中血栓素合成及反应不足。

Deficient thromboxane synthesis and response in platelets from premature infants.

作者信息

Israels S J, Odaibo F S, Robertson C, McMillan E M, McNicol A

机构信息

Departments of Pediatrics, Manitoba Institute of Cell Biology, University of Manitaba, Winnipeg, Canada.

出版信息

Pediatr Res. 1997 Feb;41(2):218-23. doi: 10.1203/00006450-199702000-00011.

DOI:10.1203/00006450-199702000-00011
PMID:9029642
Abstract

In vitro function of cord blood platelets from 35 premature infants (gestational age 32 +/- 3.2 wk) was compared with that of 12 full-term infants and 14 adult control subjects. In comparison with adult platelets, preterm platelets showed impaired aggregation, in response to thrombin, collagen, ADP, and U46619 [a stable analog of thromboxane A2 (TxA2)], and impaired [14C]serotonin secretion in response to collagen and U46619. The production of TxB2 (the stable TxA2 metabolite) in response to collagen was reduced in preterm platelets (30.2 +/- 5.5 ng/mL) compared with full-term (52.7 +/- 12.6 ng/mL) or adult control platelets (132.3 +/- 38.7 ng/mL). The deficient TxB2 production and U46619 response prompted further investigation of TxA2 receptor number and binding characteristics. Immunoblotting using an anti-TxA2 receptor antibody (anti-P2) identified a single, identical 55-kD band in solubilized membranes of control, full-term, and preterm platelets. Flow cytometry using anti-P2 produced histograms that did not differ between adults and neonates. Ligand binding studies using [3H]U46619 were carried out on 10 samples from each group. Scatchard analysis yielded a single class of binding sites with no significant difference among the Kd values (85 +/- 16 versus 99 +/- 12 versus 100 +/- 12 nM) or number of binding sites per platelet (1876 +/- 460 versus 2450 +/- 478 versus 2777 +/- 536) for preterm and full-term infants and adults. Therefore platelets of preterm infants show impaired TxA2 production and response. The poor response is not related to altered binding characteristics of the TxA2 receptor but may lie in the postreceptor signal transduction pathway.

摘要

将35名早产儿(胎龄32±3.2周)的脐血血小板的体外功能与12名足月儿及14名成人对照者的进行了比较。与成人血小板相比,早产血小板对凝血酶、胶原、ADP和U46619[血栓素A2(TxA2)的稳定类似物]的聚集反应受损,对胶原和U46619的[14C]5-羟色胺分泌受损。与足月儿(52.7±12.6 ng/mL)或成人对照血小板(132.3±38.7 ng/mL)相比,早产血小板对胶原的TxB2(稳定的TxA2代谢产物)生成减少(30.2±5.5 ng/mL)。TxB2生成不足及对U46619反应不佳促使对TxA2受体数量及结合特性进行进一步研究。使用抗TxA2受体抗体(抗P2)的免疫印迹在对照、足月儿和早产血小板的溶解膜中鉴定出一条单一、相同的55-kD条带。使用抗P2的流式细胞术产生的直方图在成人和新生儿之间无差异。对每组的10个样本进行了使用[3H]U46619的配体结合研究。Scatchard分析得出单一类结合位点,早产和足月儿及成人的Kd值(85±16对99±12对100±12 nM)或每个血小板的结合位点数(1876±460对2450±478对2777±536)之间无显著差异。因此,早产儿的血小板显示TxA2生成及反应受损。反应不佳与TxA2受体结合特性改变无关,而可能在于受体后信号转导途径。

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