异丙肾上腺素致SD大鼠心肌损伤标志物的研究

Research on Biomarkers in Rats with Cardiac Injury Induced by Isoprenaline

探讨心肌肌钙蛋白（cardiac troponin I,c Tn I）、心脏型脂肪酸结合蛋白（heart fatty acid-binding Protein,H-FABP）和C反应蛋白（C-reactive protein,CRP）作为标志物在临床前毒理实验中诊断早期心肌损伤的应用价值。雄性SD大鼠单次腹腔注射给予异丙肾上腺素0.5、5、50 mg/kg,于给药后1、3、6、12、24 h采血及解剖。采用液态悬浮芯片系统Luminex测定血清c Tn I,ELISA法测定H-FABP与CRP水平,全自动生化分析仪测定血清谷草转氨酶（AST）和肌酸激酶同工酶（CK-MB）活力,观察大鼠心脏组织病理学改变。通过ROC曲线比较给药后1-24 h各标志物的灵敏度与特异性。c Tn I在3-24 h内给药组与对照组相比有不同程度的升高;H-FABP在1-3 h时给药组明显高于对照组,早于可见病理损伤出现的时间;CRP在24 h时中、高剂量组略有升高。大鼠血清中c Tn I、H-FABP、CRP、AST、CK-MB的ROC曲线下面积AUC分别为：0.821、0.763、0.584、0.741、0.742。在本心肌损伤模型中,c Tn I和H-FABP诊断效能可能高于传统心肌酶谱,而CRP未表现出对早期心肌损伤的诊断价值。

This study is focused on the application value of taking cardiac troponin I（ c Tn I）,Heart Fatty Acid-binding Protein（ H-FABP） and C-reactive protein（ CRP） which used as the biomarkers to diagnose preclinical cardiac injury. Male SD rats were treated a single i. p. injection of isoprenaline at levels of 0. 5,5 or 50 mg / kg,and were evaluated at 1,3,6,12,24 h post-dosing for testing biomarkers and cardiac histology. Cardiac troponin I（ c Tn I） levels was measured by luminex,Heart fatty acid-binding protein（ H-FABP） and C-reactive protein（ CRP） were measured by enzyme-linked immunosorbent assay（ ELISA）. The activities of glutamic-oxalacetic transaminase（ AST） and creatine kinase MB（ CK-MB） were determined by automatic biochemical analyzer. Rat cardiac histopathology were examined under microscope. Receiver operator characteristics（ ROC） analysis was used to compare sensitivity and specificity of each biomakers. The mean levels of c Tn I were significant elevated at 3 to 24 h in isoprenaline group. The H-FABP levels of serum were greater than that of controls at 1 to 3 h,earlier than visible cardiac injuries observed. CRP was increased at24 h in isoprena group. In ROC analysis,the area under the curve of c Tn I,H-FABP,CRP,AST and CK-MB were 0. 821,0. 763,0. 584,0. 741,0. 742,respectively. In this model,the diagnostic value of c Tn I and H-FABP are higher than other classical indicators,while CRP showing no diagnostic value to the early cardiac injury.