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卡维地洛减弱肥厚心肌能量代谢向胚胎型转换的分子机制(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2003年第3期
页码:
208-211
栏目:
实验研究
出版日期:
2003-05-01

文章信息/Info

Title:
Molecular mechanism of Carvedilol on attenuating the reversion back towards fetal energy metabolism occurring with the development of cardiac hypertrophy
作者:
胡琴1; 李隆贵2
1.贵阳医学院附属医院心内科,贵州 贵阳550001;2.第三军医大学新桥医院心内科,重庆400037
Author(s):
HUQin1; LILong-gu2
1.Department of Cardiology,Affiliated Hospital,Gui yang Medical College,Gui yang,Gui zhou 550001,2.Department of Cardiology,Xin qiao Hospital,Third Military Medical University, Chong qing400037,China
关键词:
卡维地洛; 压力超负荷; 脂肪酸氧化; 能量代谢胚胎型转换
Keywords:
Carvedilol; pressure overload; fatty acid oxidation; reversion of the metabolism towards fetal pattern
分类号:
R542.2;R364.2
DOI:
-
文献标识码:
A
摘要:
目的:观察压力负荷性大鼠肥厚心肌能量代谢的转换模式及卡维地洛的作用,探讨卡维地洛减弱压力负荷性心肌能量代谢胚胎型转换的分子调控机制。方法:用卡维地洛治疗腹主动脉缩窄术后4周的雄性Waster大鼠,治疗12周后观察假手术组、腹主动脉缩窄组和卡维地洛干预组大鼠血流动力学参数、心室重构指标、血清和心肌游离脂肪酸的含量及肌型肉毒碱棕榈酰转移酶I(M-CPT-I)和中链脂酰辅酶A脱氢酶(MCAD)mRNA的表达变化。结果:术后16周大鼠左室心肌明显肥厚,血清和心肌游离脂肪酸的含量增加,左室肥厚心肌M-CPT-I和MCADmRNA的表达下调。卡维地洛治疗12周后能够明显改善上述变化。结论:压力负荷性大鼠肥厚心肌能量代谢模式发生胚胎型转换;卡维地洛能够减少左室心肌脂肪酸氧化限速酶和关键酶的基因表达,减弱心肌胚胎型能量代谢的转换。
Abstract:
AIM:To study the reversion of the metabolic gene expression pattern of hypertrophic cardiac muscle and role of Carvedilol,and to explore the molecular regulation mechanism of Carvedilol on attenuating the reversion back towards fetal energy metabolism occurring with the development of cardiac hypertrophy.METHODS:A model of hypertrophy induced by coarctation of abdominal aorta (CAA) in male wistar rats was used to investigate the hemodynamics, ventricular remodeling parameters,free fatty acid in blood serum and cardiac myocyte and expressions of muscle carnitine palmitoyltransferase I(M-CPT-I) and medium chain acyl-CoA dehydrogenase (MCAD) mRNA in the experimental animals at 16-week after operation(CAA) and sham operation SH and Carvedilol intervention group(CAR).RESULTS:The left ventricle showed significant hypertrophy 16 weeks after the operation, fatty acids accumulated significantly and levels of M-CPT-I and MCAD mRNA continued to be downregulated during hypertrophic growth. Carvedilol could attenuate these changes after 12 week therapy. CONCLUSION:Pressure overload downregulates expression of rate-limiting enzyme and key enzyme of fatty acid oxidation,leading to the metabolic fetal switch of energy substrate. Carvedilol attenuates this reversion of the metabolic gene expression pattern towards fetal levels through up-regulating expressions of M-CPT-I and MCAD mRNA.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2002-7-8.
更新日期/Last Update: 2003-05-01