RESUMO
Yi-Qi-Huo-Xue Decoction (YQHX) is the recombination of Dang-Gui-Bu-Xue Decoction (DBD), which is one of the well-known traditional Chinese Medicine (TCM) prescription, and has long been shown to have significant protective effects against myocardial ischemic injury. In previous studies, we found that YQHX could regulate lipid and glucose metabolism, promote angiogenesis, attenuate inflammatory response, and ameliorate left ventricular function in myocardial ischemia rat models. However, the underlying mechanism of how YQHX involves in lipid metabolism remains unclear so far. In this study, the underlying mechanism of YQHX in lipid metabolism disorders was elucidated in a myocardial ischemia rat model and a hypoxia-induced H9c2 cell injury model. YQHX (8.2 g·kg) and positive-control drug trimetazidine (10 mg·kg) were administered daily on the second day after left anterior descending (LAD) operation. At 7 days and 28 days after surgery, changes of cardiac morphology, structure, and function were evaluated by H&E staining and echocardiography, respectively. The plasma lipid levels and mitochondrial ATP content were also evaluated. Western blot and RT-PCR were used to determine the protein and mRNA expressions of AMPK, PGC-1α, CPT-1α, and PPARα. YQHX improved cardiac function and ameliorated lipid metabolism disorders. Furthermore, YQHX increased the expression of p-AMPK, PGC-1α, and CPT-1α without changing PPARα in ischemic rat myocardium. In vitro, YQHX activated the protein and mRNA expression of PGC-1α, CPT-1α, and PPARα in hypoxia-induced H9c2 cells injury, whereas AMPK inhibitor Compound c blocked the effects of YQHX. Taken together, the results suggest that YQHX reduces lipid metabolism disorders in myocardial ischemia via the AMPK-dependent signaling pathway.
RESUMO
<p><b>OBJECTIVE</b>To observe the dynamic change of apoptosis and proliferation of cardiac muscle cells (CMC) after being induced by Angiotensin II (Ang I), and the effect of TCM herbs for supplementing qi and/ or activating blood circulation on it.</p><p><b>METHODS</b>The cultured CMC of SD suckling rat were treated by Ang II, and the amplitude, rhythm and frequency of cell pulsation, the protein content, area size and apoptosis of cells at various phases as well as the influence of TCM herbs afterwards were determined by image pattern analysis system, flow cytometry and biochemical assay.</p><p><b>RESULTS</b>In the model group, cell pulsation showed quickened frequency from the 24th to 48th hr after Ang II treatment with the highest amplitude at the 24th hr; the cell area enlarged at the 24th hr, the enlargement became evident at the 48hr. Cell content of protein increased at the 24th hr, which reached to its peak at the 48th hr; an increasing trend of cell number was shown from the 12th to 48th hr; cell apoptosis started to appear at the 24th hr, it increased gradually from the 48th to 72th hr, and reached to the peak at the 72th hr (P < 0.05 or P < 0.01). All the Chinese herbs, both for supplementing qi and/or activating blood circulation, especially when they were used in combination, showed favourable preventive and therapeutic effect on CMC (P < 0.05 or P < 0.01), either at the early phase (24-48th hrs) mainly manifesting hypertrophy and proliferation or the late phase (48-96th hrs) mainly manifesting apoptosis.</p><p><b>CONCLUSION</b>There exist characterized phasic windows of CMC after being treated by Ang II, the window of hypertrophy-proliferation phase and the window of cell apoptosis phase. When CMC were mainly in hypertrophic manner, myocardial hypertrophy may appear. Cell apoptosis may be one of the mechanisms for turning myocardial hypertrophy to heart failure, and it could be improved by Chinese herbs for supplementing qi and/or activating blood circulation.</p>
