O'Brien P J, Dameron G W, Beck M L, Kang Y J, Erickson B K, Di Battista T H, Miller K E, Jackson K N, Mittelstadt S
Human Safety Department, Procter and Gamble Company, Cincinnati, Ohio, USA.
Lab Anim Sci. 1997 Oct;47(5):486-95.
A reliable serum assay that can discriminate between cardiac and skeletal muscle injury is not available for diagnostic use in laboratory animals. We tested and supported the hypotheses that serum cardiac troponin T (cTnT) was widely applicable in laboratory animals as a biomarker of cardiac injury arising from various causes; that it increased in proportion to severity of cardiac injury; and that it was more cardiospecific than creatine kinase (CK) or lactate dehydrogenase (LD) isozyme activities. In canine and rat models of myocardial infarction, cTnT concentration increased 1,000- to 10,000-fold and was highly correlated with infarct size within 3 h of injury. Serum CK and LD isozymes were substantially less effective biomarkers and, in contrast to cTnT, were ineffective markers in the presence of moderate skeletal muscle injury, with resulting serum CK activity > 5,000 U/L. Using these animal models, and mouse and ferret models, we also showed cTnT to be an effective biomarker in doxorubicin cardiotoxicosis, traumatic injury, ischemia, and cardiac puncture. Reference range serum concentrations for all species were at the detection limit of the assay, except those for mice, in which they were slightly increased, possibly because mice were used to generate assay monoclonal antibodies. We conclude that cTnT is a powerful biomarker in laboratory animals for the sensitive and specific detection of cardiac injury arising from various causes.
在实验动物中，目前尚无一种可靠的血清检测方法可用于鉴别心脏和骨骼肌损伤。我们对以下假设进行了测试并提供了支持：血清心肌肌钙蛋白T（cTnT）可作为各种原因引起的心脏损伤的生物标志物，广泛应用于实验动物；其升高幅度与心脏损伤的严重程度成正比；并且它比肌酸激酶（CK）或乳酸脱氢酶（LD）同工酶活性更具心脏特异性。在犬和大鼠心肌梗死模型中，cTnT浓度在损伤后3小时内增加了1000至10000倍，且与梗死面积高度相关。血清CK和LD同工酶作为生物标志物的效果要差得多，与cTnT不同的是，在存在中度骨骼肌损伤（导致血清CK活性>5000 U/L）时，它们作为标志物无效。利用这些动物模型，以及小鼠和雪貂模型，我们还表明cTnT在阿霉素心脏毒性、创伤性损伤、缺血和心脏穿刺中是一种有效的生物标志物。除小鼠外，所有物种的参考范围血清浓度均处于检测限，小鼠的参考范围血清浓度略有升高，可能是因为小鼠被用于制备检测单克隆抗体。我们得出结论，cTnT是实验动物中一种强大的生物标志物，可用于灵敏且特异地检测各种原因引起的心脏损伤。
