Lorenz R L, Uedelhoven W M, Fischer S, Ruetzel A, Weber P C
Medizinische Klinik Innenstadt, Universität München, F.R.G.
Biochim Biophys Acta. 1989 Dec 8;993(2-3):259-65. doi: 10.1016/0304-4165(89)90174-8.
Urinary immunoreactive thromboxane (irTXB2) has been found helpful in acute settings with altered renal, but also extrarenal thromboxane formation. As only trace amounts of systemically formed thromboxane are excreted unmetabolized, the nature of urinary irTXB2 was explored. The two most abundant metabolites of systemic thromboxane, 2,3-dinor-TXB2 and 11-dehydro-TXB2, crossreacted about 70% and less than 1%, respectively, with a widely used thromboxane antiserum. After solid-phase extraction of urine samples and separation on reversed-phase HPLC, the bulk of immunoreactivity always eluted as one peak shown to correspond to 2,3-dinor-TXB2. Much less was found in fractions where TXB2 eluted. Therefore, urines were read against calibration curves constructed with 2,3-dinor-TXB2. This direct estimation gave good recoveries for standard 2,3-dinor-TXB2 and correlated well, both in healthy controls and in patients at increased risk or with overt vascular disease, to values obtained after solid phase extraction, purification on reversed-phase HPLC and quantitation by either gas-chromatography mass-spectrometry or radioimmunoassay. Patients with multiple cardiovascular risk factors but free from detectable vascular disease excreted significantly more irTXB2 than age-matched controls with non-vascular conditions or normals. Therefore, urinary irTXB2 measured with this antiserum represents 2,3-dinor-TXB2, reflecting the systemic formation of TXB2. This simple approach is feasible for screening thromboxane formation in large series of patients. Its acumen in detecting the early development of vascular disease and its relation to established risk factors deserves large-scale prospective testing.
尿免疫反应性血栓素（irTXB2）已被证明在肾脏以及肾外血栓素生成改变的急性情况下很有帮助。由于全身生成的血栓素只有微量以未代谢形式排出，因此对尿irTXB2的性质进行了探索。全身血栓素的两种最丰富的代谢产物，2,3-二去甲血栓素B2（2,3-dinor-TXB2）和11-脱氢血栓素B2（11-dehydro-TXB2），与一种广泛使用的血栓素抗血清的交叉反应率分别约为70%和不到1%。在对尿样进行固相萃取并在反相高效液相色谱上分离后，大部分免疫反应性总是作为一个峰洗脱，显示对应于2,3-二去甲血栓素B2。在血栓素B2洗脱的部分中发现的要少得多。因此，尿液是根据用2,3-二去甲血栓素B2构建的校准曲线进行读数的。这种直接估计对标准2,3-二去甲血栓素B2有良好的回收率，并且在健康对照以及有增加风险或明显血管疾病的患者中，与固相萃取、反相高效液相色谱纯化以及通过气相色谱-质谱法或放射免疫测定法定量后获得的值相关性良好。有多种心血管危险因素但无可检测到的血管疾病的患者排出的irTXB2明显多于年龄匹配的无血管疾病的对照或正常人。因此，用这种抗血清测量的尿irTXB2代表2,3-二去甲血栓素B2，反映了血栓素B2的全身生成。这种简单的方法对于在大量患者中筛选血栓素生成是可行的。其在检测血管疾病早期发展方面的敏锐性及其与既定危险因素的关系值得进行大规模前瞻性测试。
