O'Brien P J, Smith D E C, Knechtel T J, Marchak M A, Pruimboom-Brees I, Brees D J, Spratt D P, Archer F J, Butler P, Potter A N, Provost J P, Richard J, Snyder P A, Reagan W J
Safety Sciences Europe, Sandwich, Kent CT1 3NJ, UK. Peter.O'
Lab Anim. 2006 Apr;40(2):153-71. doi: 10.1258/002367706776319042.
This study directly demonstrates that cardiac troponin I (cTnI) is a sensitive, specific, and persistent biomarker in laboratory animals. Histopathological and pathophysiological cardiac changes in dogs, rats and mice correlated with increased serum cTnI with various cardiac inotropic agents, and cardiotoxic drugs and with cardiac arrhythmias, tachycardia, cardiac effusion with dyspnoea, and ageing. A comparison of six immunoassays for cTnI and cardiac troponin T (cTnT) to detect and monitor cardiac injury in a rodent model indicated that enzyme-linked immunosorbent (Life Diagnostics Inc and TriChem Resources Inc, West Chester, Philadelphia, USA) and Immulite (Diagnostic Products Corporation, Llanberis, UK) assays had low sensitivity and less than 1% of the dynamic range of Centaur (Bayer Healthcare Diagnostics, Newbury, UK) cTnI and Elecsys (Roche Diagnostics, Basel, Switzerland) and M8 (Bioveris Europe, Whitney, UK) cTnT assays. In dogs, however, the Immulite assay was effective and correlated with the Centaur. Serum concentrations were highly correlated but 10-fold lower for cTnT compared with cTnI with cardiac injury. Centaur assay also detected cTnI in myocardium from marmosets, swine, cattle, and guinea pigs, indicating it to be candidate cardiac biomarker for these species as well. Purified rat cTnI was 50% more reactive than purified human cTnI in the Centaur assay. In the rat, an age- and gender-dependent variation in serum cTnI was found. Male rats aged six and eight months had a 10-fold greater serum cTnI than age-matched females and three-month-old rats. These increases correlated with minimal histopathological change. Isoproterenol-induced serum cTnI increased up to 760-fold the minimal detectable concentration of 0.07 microg/L, within 4-6 h and decreased with a half-life of 6 h, with an expected return to baseline of 60 h. Severity of histopathological change correlated with serum cTnI during the ongoing injury.
本研究直接证明，心肌肌钙蛋白I（cTnI）在实验动物中是一种敏感、特异且持续存在的生物标志物。犬、大鼠和小鼠的组织病理学和病理生理学心脏变化与各种强心剂、心脏毒性药物以及心律失常、心动过速、伴有呼吸困难的心脏积液和衰老导致的血清cTnI升高相关。在啮齿动物模型中，对六种检测和监测心脏损伤的cTnI和心肌肌钙蛋白T（cTnT）免疫测定法进行比较，结果表明，酶联免疫吸附法（美国费城韦斯特切斯特的Life Diagnostics公司和TriChem Resources公司）和Immulite法（英国兰贝里斯的Diagnostic Products Corporation公司）的灵敏度较低，其动态范围不到拜耳医疗保健诊断公司（英国纽伯里）的Centaur cTnI测定法以及罗氏诊断公司（瑞士巴塞尔）的Elecsys和Bioveris Europe公司（英国惠特尼）的M8 cTnT测定法动态范围的1%。然而，在犬中，Immulite测定法是有效的，且与Centaur测定法相关。血清浓度高度相关，但心脏损伤时cTnT的浓度比cTnI低10倍。Centaur测定法还在狨猴、猪、牛和豚鼠的心肌中检测到了cTnI，这表明它也是这些物种的候选心脏生物标志物。在Centaur测定法中，纯化的大鼠cTnI的反应性比纯化的人cTnI高50%。在大鼠中，发现血清cTnI存在年龄和性别依赖性差异。6个月和8个月大的雄性大鼠血清cTnI比年龄匹配的雌性大鼠和3个月大的大鼠高10倍。这些升高与最小的组织病理学变化相关。异丙肾上腺素诱导的血清cTnI在4 - 6小时内增加至最低可检测浓度0.07μg/L的760倍，并以6小时的半衰期下降，预计60小时后恢复至基线水平。在持续损伤期间，组织病理学变化的严重程度与血清cTnI相关。
