Improvement of mechanical heart function by trimetazidine in db/db mice.
Improvement of mechanical heart function by trimetazidine in db/db mice.
复制标题
曲美他嗪改善 db/db 小鼠机械心脏功能
DOI：
10.1038/aps.2010.31
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发表时间：
2010-05
影响因子：
8.2
通讯作者：
Wang, Dao-wen
中科院分区：
文献类型：
--
作者：
Li, Yuan-jing;Wang, Pei-hua;Chen, Chen;Zou, Ming-hui;Wang, Dao-wen
关键词：
目的：探讨抗氧化剂和代谢调节剂曲美他嗪对db/db小鼠心脏功能和糖尿病心肌病发生的影响。方法：给予db/db小鼠曲美他嗪治疗8周。通过将 Millar 导管插入左心室来测量心脏功能，并评估心肌中的氧化应激和 AMP 激活蛋白激酶（AMPK）活性。结果：与正常 C57 小鼠相比，未治疗的 db/db 小鼠表现出心功能显着下降。心肌中的氧化应激和脂质沉积显着增加，同时 AMPK 失活和过氧化物酶体增殖物激活受体辅激活因子 1α (PGC-1α) 表达增加。曲美他嗪显着改善 db/db 小鼠心脏的收缩和舒张功能，并导致心肌细胞中活性氧的产生和脂肪酸沉积减少。曲美他嗪还引起 db/db 小鼠心脏中的 AMPK 激活并降低 PGC-1α 表达。结论：数据表明曲美他嗪通过减弱脂毒性和改善心脏氧化状态显着改善 db/db 小鼠的心脏功能。 AMPK 的激活和 PGC-1α 表达的减少参与了这一过程。此外，我们的研究表明曲美他嗪可以抑制糖尿病心肌病的发展，这值得进一步的临床研究。
Aim:To investigate the influence of trimetazidine, which is known to be an antioxidant and modulator of metabolism, on cardiac function and the development of diabetic cardiomyopathy in db/db mouse.Methods:Trimetazidine was administered to db/db mice for eight weeks. Cardiac function was measured by inserting a Millar catheter into the left ventricle, and oxidative stress and AMP-activated protein kinase (AMPK) activity in the myocardium were evaluated.Results:Untreated db/db mice exhibited a significant decrease in cardiac function compared to normal C57 mice. Oxidative stress and lipid deposition were markedly increased in the myocardium, concomitant with inactivation of AMPK and increased expression of peroxisome proliferator-activated receptor coactivator-1α (PGC-1α). Trimetazidine significantly improved systolic and diastolic function in hearts of db/db mice and led to reduced production of reactive oxygen species and deposition of fatty acid in cardiomyocytes. Trimetazidine also caused AMPK activation and reduced PGC-1α expression in the hearts of db/db mice.Conclusion:The data suggest that trimetazidine significantly improves cardiac function in db/db mice by attenuating lipotoxicity and improving the oxidation status of the heart. Activation of AMPK and decreased expression of PGC-1α were involved in this process. Furthermore, our study suggests that trimetazidine suppresses the development of diabetic cardiomyopathy, which warrants further clinical investigation.
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影响因子：
5
作者：
Kewalramani, Girish;An, Ding;Rodrigues, Brian
通讯作者：
Rodrigues, Brian
DOI：
10.1152/ajpendo.2000.279.5.e1104
发表时间：
2000-11-01
影响因子：
5.1
作者：
Belke, DD;Larsen, TS;Severson, DL
通讯作者：
Severson, DL
影响因子：
15.9
作者：
Finck, BN;Lehman, JJ;Kelly, DP
通讯作者：
Kelly, DP
DOI：
10.1111/j.1432-1033.2004.04151.x
发表时间：
2004-06-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Clark, H;Carling, D;Saggerson, D
通讯作者：
Saggerson, D
影响因子：
37.8
作者：
Duncan, Jennifer G.;Fong, Juliet L.;Kelly, Daniel P.
通讯作者：
Kelly, Daniel P.