CPU86017 and its enantiomers inhibit abnormal gene expression of calcineurin and NFκB in rat cardiomyopathy induced by L-thyroxin
- VernacularTitle:CPU86017及其旋光异构体对L-甲状腺素致大鼠心肌病异常的calcineurin和NFκB基因表达的抑制作用
- Author:
Minyou QI
;
Huijing XIA
;
Dezai DAI
;
Xiaoyun TANG
;
Wei SU
;
Can ZHANG
- Publication Type:Journal Article
- Keywords:
CPU86017;
enantiomers;
L-thyroxin;
cardiac hypertrophy;
calcineurin
- From:
Chinese Journal of Clinical Pharmacology and Therapeutics
2006;11(4):392-397
- CountryChina
- Language:Chinese
-
Abstract:
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.
