心肌肌钙蛋白I的测定在药物非临床安全性评价中的应用

Application of cardiac troponin I determination in non-clinical safety evaluation of drugs

目的:探讨心肌肌钙蛋白I(cardiac troponin I,cTnI)在Beagle犬多次给药毒性实验中的应用价值。方法:以心肌酶测定值及病理组织学检查结果为标准,收集184只Beagle犬案例,分为正常对照组、形态损伤组及非形态损伤组。测定各组实验动物血清cTnI含量,并对比心肌酶测定值及病理组织学检查结果。结果:形态损伤组和非形态损伤组Beagle犬血清cTnI高于正常对照组(P<0.05);形态损伤组Beagle犬血清cTnI与天冬氨酸氨基转移酶(AST)、肌酸激酶(CK)、AST/CK检测阳性结果不同,血清cTnI阳性检测率较高(P<0.01);非形态损伤组Beagle犬血清cTnI与AST检测阳性结果不同,血清AST阳性检测率较高(P<0.05),血清cTnI与CK检测阳性结果不同,血清CK阳性检测率较高(P<0.01),血清cTnI与AST/CK检测阳性结果未见明显差异。结论:cTnI在诊断Beagle犬心肌损伤上有较高的敏感性,在药物安评试验中优于传统的检测指标,并且在一定程度上能够降低误诊及漏诊率。

Objective： To investigate the application of myocardial troponin I（cTnI） in cardiotoxicity in Beagle dogs receiving repeated drug administration.Methods： Samples were collected from 184 Beagle dogs according to the results of myocardial enzymes measurements and histopathological examination of the heart.Dogs were divided into 3 groups： control,morphological injury and non-injury groups.Serum cTnI was detected in each group,and analyzed together with results of myocardial enzymes and histopathological examination.Results： Serum cTnI in drug-treted dogs with or without morphological injury was higher than that in control dogs（P 0.05）.In the morphological injury group,the positive detection rate of serum cTnI was higher（P 0.01） than that of AST,CK and AST / CK.In the morphological non-injury group,the positive detection rates of serum AST（P 0.05） and serum CK（P 0.01） were higher than that of serum cTnI;however,there was no significant difference between the serum cTnI and AST / CK.Conclusion： cTnI has high sensitivity in the diagnosis of myocardial injury in dogs.In drug safety evaluation,cTnI as a detection marker contributes to right diagnosis and avoiding delayed diagnosis in a certain extent,so it is better than the traditional indicators.