Chiabrando C, Corada M, Bachi A, Fanelli R
Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy.
Prostaglandins. 1994 Jun;47(6):409-22. doi: 10.1016/0090-6980(94)90042-6.
Urinary 2,3-dinor-thromboxane B2 (2,3-dinor-TXB2), an enzymatic degradation product of TXB2, is currently measured for evaluating in vivo thromboxane biosynthesis in rats. We simultaneously measured 2,3-dinor-TXB2 and 2,3-dinor-TXB1, another product of TXB2 metabolism, in the urine of rats by immunoaffinity extraction/gas chromatography negative ion chemical ionization mass spectrometry (GC-NICIMS). In rats under basal conditions, urinary excretion of 2,3-dinor-TXB1 was much higher than that of 2,3-dinor-TXB2 (19.22 +/- 4.86 and 1.64 +/- 0.29 ng/24 h, respectively). The relative abundance of the two metabolites in each animal was fairly constant (91.9 +/- 1.6 and 8.1 +/- 1.6% of their sum, respectively). Urinary excretion of both 2,3-dinor-TXB1 and 2,3-dinor-TXB2 increased in rats undergoing in vivo hepatic ischemia-reperfusion. Other thromboxane metabolites, including 11-dehydro-TXB2 and 11-dehydro-2,3-dinor-TXB2, were measured by GC-NICIMS in selected urines. The resulting profile was: 2,3,4,5-tetranor-TXB1 > 2,3-dinor-TXB1 >> 11-dehydro-TXB2 > 2,3-dinor-TXB2 = TXB2. This study shows that urinary 2,3-dinor-TXB1 is a suitable parameter of TXB2 biosynthesis in vivo in rats. The possible cross-reactivity of 2,3-dinor-TXB1 in immunoassays of urinary 2,3-dinor-TXB2 or even TXB2 in rats should be considered in future studies.
尿2,3 - 二去甲血栓素B2(2,3 - dinor - TXB2)是血栓素B2(TXB2)的酶促降解产物,目前用于评估大鼠体内血栓素的生物合成。我们采用免疫亲和萃取/气相色谱负离子化学电离质谱法(GC - NICIMS)同时测定了大鼠尿液中的2,3 - 二去甲血栓素B2和2,3 - 二去甲血栓素B1(TXB2代谢的另一种产物)。在基础条件下的大鼠中,2,3 - 二去甲血栓素B1的尿排泄量远高于2,3 - 二去甲血栓素B2(分别为19.22±4.86和1.64±0.29 ng/24 h)。每只动物体内这两种代谢产物的相对丰度相当恒定(分别占它们总和的91.9±1.6和8.1±1.6%)。在经历体内肝脏缺血再灌注的大鼠中,2,3 - 二去甲血栓素B1和2,3 - 二去甲血栓素B2的尿排泄量均增加。通过GC - NICIMS在选定的尿液中测定了其他血栓素代谢产物,包括11 - 脱氢 - TXB2和11 - 脱氢 - 2,3 - 二去甲血栓素B2。所得图谱为:2,3,4,5 - 四去甲血栓素B1>2,3 - 二去甲血栓素B1>>11 - 脱氢 - TXB2>2,3 - 二去甲血栓素B2 = TXB2。本研究表明,尿2,3 - 二去甲血栓素B1是大鼠体内TXB2生物合成的合适参数。在未来的研究中应考虑2,3 - 二去甲血栓素B1在大鼠尿2,3 - 二去甲血栓素B2甚至TXB2免疫测定中可能存在的交叉反应性。