11-脱氢血栓烷B2：在人体循环中血栓烷A2形成的定量指标。,Proceedings of the National Academy of Sciences of the United States of America

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11-脱氢血栓烷B2：在人体循环中血栓烷A2形成的定量指标。
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 1986-08-01 , DOI: 10.1073/pnas.83.16.5861
F. Catella , D. Healy , J. A. Lawson , G. A. FitzGerald

在人血浆中，11-脱氢血栓烷（TX）B2是主要的长寿代谢物（t1 / 2 45分钟），由注入的TXB2（生物活性TXA2的水合产物）形成。TXB2本身的血浆浓度容易被离体血小板激活所混淆，并且理论上，该化合物的酶促衍生物（不需在全血中形成）将更准确地反映出TXA2在体内的形成。为了解决这个假设，我们使用毛细管气相色谱/负离子化学电离质谱技术开发了一种灵敏的11-脱氢TXB2和TXB2检测方法。我们确定全血形成红细胞中非酶促形成11-脱氢-TXB2的能力较小。然而，11-脱氢-TXB2的非酶形成对其作为TX生物合成指标的应用没有实际限制。（i）在插入时以及之后的30、60、90、180和240分钟时通过留置导管从健康志愿者身上抽取血液；（ii）在0时以及之后的90和240分钟时通过单独的静脉穿刺。通过导管在基线处抽取的血浆TXB2（66 +/- 63 pg / ml）大大大于血浆中内源TXB2的最大估计值（1-2 pg / ml）[Patrono，C.，Ciabattoni，G.，Pugliese ，F.，Perruci，A.，Blair，IA和FitzGerald，GA（1986）J.Clin.Biol.215：403-10。投资。[第77卷，第590-594页]，并随时间增加幅度和方差（240分钟时为339 +/- 247 pg / ml）。相反，在顺序的导管样品或通过单独的静脉穿刺抽取的样品中，11-脱氢-TXB2没有明显变化。用325 mg阿司匹林预处理可降低志愿者的基础血浆浓度。此外，严重的动脉粥样硬化患者尿2,3-dinor-TXB2升高的浓度范围显着高于健康受试者（0.9-1.8 pg / ml）（5-50 pg / ml，P小于0.01）。）。与11-dehydro-13,14-dihydro-15-keto-TXB2或2,3-dinor-TXB2代谢产物相比，最近遭受肺栓塞的患者中11-dehydro-TXB2的浓度增加的程度更大在血浆中。这些结果表明血浆TXB2容易通过离体血小板活化而混淆。测量TXB2的酶代谢产物可最大程度地减少此问题。11-脱氢代谢物是检测人类血液中TXA2逐步释放的最合适的分析目标，

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11-Dehydrothromboxane B2: a quantitative index of thromboxane A2 formation in the human circulation.

In human plasma, 11-dehydrothromboxane (TX) B2 is a major long lived metabolite (t1/2 45 min) formed from infused TXB2, the hydration product of biologically active TXA2. Plasma concentrations of TXB2 itself are readily confounded by ex vivo platelet activation and, theoretically, an enzymatic derivative of this compound, not subject to formation in whole blood, would more accurately reflect TXA2 formation in vivo. To address this hypothesis, we developed a sensitive assay for both 11-dehydro-TXB2 and TXB2, using capillary gas chromatography/negative-ion chemical ionization mass spectrometry. We established that whole blood possesses a minor capacity to form 11-dehydro-TXB2, attributable to nonenzymatic formation in erythrocytes. However, the nonenzymatic formation of 11-dehydro-TXB2 was not a practical limitation to its use as an index of TX biosynthesis. Blood was drawn from healthy volunteers (i) via an indwelling catheter at the time of insertion and at 30, 60, 90, 180, and 240 min thereafter and (ii) via separate venipunctures at 0 time and at 90 and 240 min thereafter. Plasma TXB2 drawn via the catheter at baseline (66 +/- 63 pg/ml) was substantially greater than the maximal estimate of endogenous TXB2 (1-2 pg/ml) in plasma [Patrono, C., Ciabattoni, G., Pugliese, F., Perruci, A., Blair, I. A. & FitzGerald, G. A. (1986) J. Clin. Invest. 77, 590-594] and increased in magnitude and variance over time (339 +/- 247 pg/ml at 240 min). By contrast, 11-dehydro-TXB2 did not change significantly in the sequential catheter samples or in the samples drawn by separate venipuncture. Basal plasma concentrations in volunteers were depressed by pretreatment with 325 mg of aspirin. Furthermore, the range of concentrations in patients with severe atherosclerosis in whom urinary 2,3-dinor-TXB2 was increased was significantly higher (5-50 pg/ml, P less than 0.01) than in healthy subjects (0.9-1.8 pg/ml). Concentrations of 11-dehydro-TXB2 were increased in patients who had recently suffered a pulmonary embolism to a greater extent than either the 11-dehydro-13,14-dihydro-15-keto-TXB2 or the 2,3-dinor-TXB2 metabolites in plasma. These results indicate that plasma TXB2 is readily confounded by platelet activation ex vivo. Measurement of enzymatic metabolites of TXB2 minimizes this problem. The 11-dehydro metabolite is the most appropriate analytic target to detect phasic release of TXA2 in the human circulation, such as might occur in human syndromes of platelet activation.

更新日期：2019-11-01

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