中文摘要：

目的：研究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基因改变,并比较CPU86017及其旋光异构体对它们的作用.方法：大鼠随机分成7组,每日给予L-甲状腺素（0.2 mg·kg^-1, sc） 共 10 d 造成心肌病模型,CPU86017及其旋光异构体（SR、SS、RS、RR）（4 mg·kg^-1, sc）在 d 6 连续给药 5 d.动物处死后测定心脏指数,取大鼠心脏测定心肌组织中氧化应激指标,NO和iNOS的活力,大鼠左心室心肌Calcineurin、NF-κB的基因表达由半定量逆转录酶PCR方法测定.结果：L-甲状腺素致大鼠心肌病模型组心肌明显肥大,氧化应激增强,NO含量减少,iNOS活力增强,Calcineurin和NF-κB基因表达上调.给予CPU86017及其旋光异构体能不同程度地改善心肌中NO含量及iNOS活力,减轻氧化应激,可以下调这些基因的表达,其中SR比其它旋光异构体疗效好.结论：Calcineurin 和NF-κB可能对L-甲状腺素所致大鼠心肌病中细胞内钙调节起着重要的作用,CPU86017及其旋光异构体SR对L-甲状腺素所致大鼠心肌病具有保护作用,该作用与抑制心肌Calcineurin、NF-κB基因的表达、抑制NOS及抗氧化有关.

英文摘要：

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.