心肌损伤生物标志物在毒理学实验中的应用进展

Progress in application of biomarkers of myocardial injury in toxicity study

心肌损伤生物标志物的检测在心脏疾病临床诊断上被广泛应用,但是在新药的非临床安全评价方面,心肌损伤标志物的应用相对滞后。目前中国、美国、经济合作发展组织(OECD)的新药安全评价指导原则推荐的检测心脏功能的指标为谷草转氨酶(AST)、乳酸脱氢酶(LDH)和肌酸激酶(CK)。但是上述指标敏感性差(如AST)以及存在同工酶(如LDH和CK),所以不能特异灵敏地反映心脏的功能。目前国际上高度推崇采用敏感效应生物标志物来监测心脏的靶器官毒性。近年来肌红蛋白(Mb)、脑型钠尿肽(BNP)、心肌肌钙蛋白(cTn)对心肌损伤的检测展现了良好的应用价值,本文将对上述3项国内外研究最热点的心肌损伤生物标志物进行阐述。

The biomarkers of myocardial injury are used widely in clinical diagnosis of heart diseases. However, application of the biomarker in drug preclinical safety evaluation is relatively less. Aspartate aminotransferase （AST）, lactate dehydrogenase （LDH） and creatine kinase （CK） are myocardial injury biomarkers recommended in China, USA, and OECD. Unfortunately, due to the slow response （e. g. , AST） and presence of isozymes （e. g. , LDH and CK） , they are not sensitive or specific for cardiac function evaluations. Recently, higher sensitive and specific biomarkers, such as myoglobulin （Mb）, B-type natriuretic peptide （BNP） and cardiac troponin （cTn） are highly recommended for assessing cardiotoxicity in preclinical safety studies; these biomarkers are discussed in details in this review.