CAJ | 학술논문

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.
목적:연구CPU86017급기선광이구체대L-갑상선소치대서심기병이상적calcineurin화 NFκB기인개변,병비교CPU86017급기선광이구체대타문적작용.방법:대서수궤분성7조,매일급여L-갑상선소(0.2 mg·kg-1, sc) 공 10 d 조성심기병모형,CPU86017급기선광이구체(SR、SS、RS、RR)(4 mg·kg-1, sc)재 d 6 련속급약 5 d.동물처사후측정심장지수,취대서심장측정심기조직중양화응격지표,NO화iNOS적활력,대서좌심실심기Calcineurin、NF-κB적기인표체유반정량역전록매PCR방법측정.결과:L-갑상선소치대서심기병모형조심기명현비대,양화응격증강,NO함량감소,iNOS활력증강,Calcineurin화NF-κB기인표체상조.급여CPU86017급기선광이구체능불동정도지개선심기중NO함량급iNOS활력,감경양화응격,가이하조저사기인적표체,기중SR비기타선광이구체료효호.결론:Calcineurin 화NF-κB가능대L-갑상선소소치대서심기병중세포내개조절기착중요적작용,CPU86017급기선광이구체SR대L-갑상선소소치대서심기병구유보호작용,해작용여억제심기Calcineurin、NF-κB기인적표체、억제NOS급항양화유관.
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.