中文摘要：

目的研究大鼠静脉注射不同剂量盐酸异丙肾上腺素后血清心肌钙蛋白Ⅰ（cTnⅠ）的动力学变化及诊断时间窗,为临床前cTnⅠ的应用提供理论依据。方法 SD大鼠单次静脉注射盐酸异丙肾上腺素0.625、1.250和2.500 mg/kg,并于给药前和给药后1、4、8、24、48和72 h分别采血,测定血清AST、LDH和CK活性及血清cTnⅠ浓度。结果各给药组大鼠给药后1 h平均血清cTnⅠ即出现显著升高,且4 h达到峰值。0.625、1.250和2.500 mg/kg剂量组大鼠血清cTnⅠ分别是对照组的272.7、523.5和1 242.0倍,呈明显的剂量依赖性;给药后48-72 h血清cTnⅠ值与对照组接近。各组给予盐酸异丙肾上腺素后4 h血清AST显著升高,且达到最大值,分别是对照组的1.3、1.6和2.1倍;给药后24-72 h,各组血清AST值均与对照组接近。给药后1-72 h血清LDH和CK未见明显改变。结论急性心肌损伤动物血清cTnⅠ升高时间早于传统心肌酶学标志物,且升高幅度较大,用于临床前药源性心肌损伤的诊断时间窗宽（1-24 h）。cTnⅠ在临床前药源性心脏毒性诊断中是较为理想的生物标志物。

英文摘要：

Objective To explore the kinetics characterization of serum cardiac troponin Ⅰ （cTnⅠ ） in the rats with acute myocardial injury induced by isoproterenol （iso） and provide theoretical basis and diagnostic window for preclinical application. Methods Sprague-Dawley rats were treated with a single intravenous injection of vehicle, 0.625, 1.250 or 2.500 mg/kg iso. Blood was collected at 1, 4, 8, 24, 48 and 72 h after iso administration for biomarkers testing. The activities ofAST, LDH and CK, and the concentration of cTnⅠ were detected. Results The peak concentration of cTnⅠ was occurred at 4 h after dose in a dose-dependent manner with 272.7 fold, 523.5 fold and 1 242.0 fold respectively in 0.625 mg/kg, 1.250 mg/kg and 2.500 mg/kg iso treated group when compared with control group. The cTnⅠ concentrations in rats treated with iso returned to baseline in 48 to 72 h post-dose. In 0.625, 1.250 or 2.500 mg/kg iso groups, the mean AST activities were increased significantly and reach the peak at 4 h post-dose, with 1.3 fold, 1.6 fold and 2.1 fold respectively when compared with control group. But it did not mean any biological significance. The mean AST activities returned to baseline for both dose groups in 24 to72 h post-dose. The mean LDH and CK activities in each iso-treated group showed no difference from concurrent controls at 1 to 72 h post-dose. Conclusion Serum cTnⅠ may be used as a wild diagnostic window （Ⅰ to 24 h） biomarker for cardiotoxicity assessment. It can be an ideal circulating biomarker for drug-induced cardiotoxicity.