Author + information
- Xie Shiyang,
- Youping Wang,
- Xiaoxiao Wang,
- Bin Li,
- Peng Chen,
- Cuiling Zhu and
- Mingjun Zhu
Although traditional Chinese medicine is widely used in the clinical treatment of heart failure (HF), the detailed mechanisms are not determined. This study focused on clarifying the effects of Shenfuyixin formula (SFYX) on the content of ATP and expression of uncoupling protein-2 (UCP-2) in myocardial tissue of rats with HF induced by myocardial infarction (MI).
HF was induced by the ligation of left anterior descending coronary artery in adult male Sprague-Dawley rats. Based on the cardiac function at week 4 after MI, all rats with myocardial infarction were randomly divided into 3 groups: HF+vehicle group; SFYX-1.76g (1.76g/kg/day) group and SFYX-8.8g (8.8g/kg/day) group. The vehicle or SFYX was given for 4 weeks by oral gavage once a day 4 weeks after MI. The left ventricular structure and function were measured by echocardiography at week 8 after MI. The content of ATP in the myocardial tissue and the mitochondrial membrane potential were determined with the bioluminescence and fluorescence probe methods, respectively. The expression of UCP-2 was determined using Western blot.
Compared to the sham group, left ventricular end-diastolic dimension (LVEDD, 9.4±0.2 vs. 7.0±0.4 mm, P<0.01) and left ventricular end-systolic dimension (LVESD, 7.7±0.2 vs. 3.5±0.5 mm, P<0.01) were significantly increased, but ejection fraction (EF, 42±2 vs. 85±4%, P<0.01) and fractional shortening (FS, 17±1 vs. 45±3%, P<0.01) decreased significantly in HF-vehicle group, which were associated with the content of ATP in the myocardial tissue and the mitochondrial membrane potential decreased significantly (ATP: 3.28±0.72 vs. 9.97±2.90 ng/mg prot, P<0.05; JC-1: 2.75±0.21 vs. 4.41±0.43, P<0.01), and the expression of UCP-2 were increased(0.14±0.01 vs. 0.05±0.02%VDAC arbitrary units, P<0.01). Compared to HF+vehicle group, SFYX enhanced systolic cardiac function (SFYX-1.76g group: EF, 52±4%, FS, 23±2%, P<0.05; SFYX-8.8g group: EF, 61±3%, FS, 29±2%, P<0.05). In addition, SFYX increased the content of ATP in the myocardial tissue and the mitochondrial membrane potential decreased (SFYX-8.8g group: ATP, 10.60±1.89 ng/mg prot, P<0.01; JC-1, 4.19±0.43, P<0.05). and the expression of UCP-2 were decreased (SFYX-1.76g group: 0.07±0.03%VDAC arbitrary units; SFYX-8.8g group: 0.08±0.04%VDAC arbitrary units, P<0.05).
Our studies showed that SFYX enhanced the content of ATP and improved cardiac function in rats with HF following MI, which were associated with the increased of mitochondrial membrane potential and the decreased expression of UCP-2. The results suggest that treatment with SFYX prevent MI-induced HF development possibly via improving mitochondrial function. [This work was supported by a grant from the National Natural Science Foundation of China (No. 81373853) to M.J.Z. * Corresponding Author].