AIM: To investigate the CPU86017 and its enantiomers inhibit abnormal gene expression of calcineurin and NFκB in rat cardiomyopathy induced by L-thyroxin and compare the effect of CPU86017(racemate) with its 4 enantiomers:(7S,13R),(7S,13S),(7R,13S),and(7R,13R)-CPU86017 in this model.METHODS: The animals were randomly divided into 7 groups.The rat hypertrophied model was produced by treatment with L-thyroxin(0.2)(mg·kg~(-1)·d~(-1)),sc for 10 d and treated with CPU86017 or its enantiomers 4(mg·kg~(-1)·d~(-1)),sc from d 6 to d 10.The changes in left ventricular(LV) weight index,redox system,and the NO and iNOS activity in the myocardium were investigated.The expression of mRNA of calcineurin、NF-κB in the left ventricle was measured.RESULTS: There were significant cardiac hypertrophy and oxidative stress in rats treated by L-thyroxin.The expression of calcineurin,NFκB mRNA were upregulated(P<(0.05),compared with that of control).After treatment with CPU86017(racemate and enantiomers),LV remodeling and the redox system were improved.CPU86017 and(7S,13R)-CPU86017 showed a better improvement on LV remodeling and the redox than the other isomers and restored the normal expression of calcineurin,NF-κB(P<(0.05),P<(0.01)),respectively.CONCLUSION: It suggested that an up-regulation of calcineurin and NFκB possibly related to the altered intracellular calcium handling system plays a role in the progression of L-thyroxin induced cardiomyopathy and CPU-86017 and its 7S,13R-CPU86017 enantiomer effectively inhibit the abnormal expression of calcineurin and NFκB genes,the NOS enzyme and oxidant stress in the cardiomyopathy.