Study on Trimetazidine on Myocardial Mitochondrial Proteomics in Heart Failure Rats with Qi-deficiency and Blood-stasis Syndrome / 世界科学技术-中医药现代化

ABSTRACT

Objective: To investigate the effects of Trimetazidine on mitochondrial proteomic alterations in heart failure rats with qi- deficiency and blood- stasis syndrome after myocardial infarction. Methods: Heart failure models were established by ligating the left anterior descending coronary artery of SD rats. Rats were randomly divided into sham group, model group, Trimetazidine group. 8 weeks after drug intervention, the mitochondrial proteomic alterations of myocardial tissue were detected by two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption/ ionization time- of- flight mass spectrometry (MALDI- TOF- MS). Furthermore, expression levels of part of the differentially expressed proteins were verified by western blot. Results: Compared with model group, 18 differentially expressed protein spots were detected in Trimetazidine group, 10 of which were successfully identified by MALDI-TOFMS. Bioinformatics analysis showed that these differential proteins were mainly associated with energy metabolism, stress reaction, oxidative damage, cyto-skeleton, cell differentiation and proliferation. Western blot results showed that the expression of Stress-70 protein and Nucleophosmin increased and the expression of ATP-αdecreased in model group. The expression of Stress- 70 protein and Nucleophosmin decreased and the expression of ATP- αincreased in Trimetazidine group, which showed the same results in proteomics. Conclusion: Trimetazidine can partly adjust proteomic alterations of myocardial mitochondrial in HF rats with qi-deficiency and blood-stasis syndrome, and its intervention mechanism may involve improving energy metabolism, relieving stress reaction and oxidative damage, as well as regulating cell differentiation and proliferation. The results of comparative proteomic analysis performed by using 2-DE and MALDI-TOF-MS are accurate, stable and reliable.