York Malcolm, Scudamore Cheryl, Brady Sally, Chen Christabelle, Wilson Sharon, Curtis Mark, Evans Gareth, Griffiths William, Whayman Matthew, Williams Thomas, Turton John
GlaxoSmithKline Research and Development, Ware, Herts, UK.
Toxicol Pathol. 2007 Jun;35(4):606-17. doi: 10.1080/01926230701389316.
The investigations aimed to evaluate the usefulness of cardiac troponins as biomarkers of acute myocardial injury in the rat. Serum from female Hanover Wistar rats treated with a single intraperitoneal (IP) injection of isoproterenol (ISO) was assayed for cardiac troponin I (cTnI) (ACS: 180SE, Bayer), cTnI (Immulite 2000, Diagnostic Products Corporation) and cardiac troponin T (cTnT) (Elecsys 2010, Roche). In a time-course study (50.0 mg/kg ISO), serum cTnI (ACS:180SE) and cTnT increased above control levels at 1 hour postdosing, peaking at 2 hours (cTnI, 4.30 microg/L; cTnT, 1.79 microg/L), and declined to baseline by 48 hours, with histologic cardiac lesions first seen at 4 hours postdosing. The Immulite 2000 assay gave minimal cTnI signals, indicating poor immunoreactivity towards rat cTnI. In a dose-response study (0.25 to 20.0 mg/kg ISO), there was a trend for increasing cTnI (ACS:180SE) values with increasing ISO dose levels at 2 hours postdosing. By 24 hours, cTnI levels returned to baseline although chronic cardiac myodegeneration was present. We conclude that serum cTnI and cTnT levels are sensitive and specific biomarkers for detecting ISO induced myocardial injury in the rat. Serum troponin values reflect the development of histopathologic lesions; however peak troponin levels precede maximal lesion severity.
这些研究旨在评估心肌肌钙蛋白作为大鼠急性心肌损伤生物标志物的效用。对单次腹腔注射异丙肾上腺素(ISO)处理的雌性汉诺威威斯塔大鼠的血清进行心肌肌钙蛋白I(cTnI)(ACS: 180SE,拜耳公司)、cTnI(免疫化学发光分析仪2000,诊断产品公司)和心肌肌钙蛋白T(cTnT)(电化学发光免疫分析仪2010,罗氏公司)检测。在一项时程研究(50.0 mg/kg ISO)中,给药后1小时血清cTnI(ACS:180SE)和cTnT升高至对照水平以上,在2小时达到峰值(cTnI,4.30μg/L;cTnT,1.79μg/L),并在48小时降至基线水平,给药后4小时首次出现心脏组织学损伤。免疫化学发光分析仪2000检测给出的cTnI信号极小,表明对大鼠cTnI的免疫反应性较差。在一项剂量反应研究(0.25至20.0 mg/kg ISO)中,给药后2小时cTnI(ACS:180SE)值有随ISO剂量水平增加而升高的趋势。到24小时,cTnI水平恢复到基线,尽管存在慢性心肌变性。我们得出结论,血清cTnI和cTnT水平是检测ISO诱导的大鼠心肌损伤的敏感且特异的生物标志物。血清肌钙蛋白值反映了组织病理学损伤的发展;然而,肌钙蛋白峰值水平先于最大损伤严重程度出现。