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[Tongxinshu Capsules improve cardiac function in rats with myocardial infarction by reducing iron overload and
1Guang'anmen Hospital, China Academy of Chinese Medical Sciences Beijing 100053, China Hebei University of Chinese Medicine Shijiazhuang 050200, China.
Abstract:
This study conducted in vivo experiments to verify the effect of Tongxinshu Capsules on cardiac function and energy metabolism remodeling in rats with myocardial infarction. The mechanism of improving the hypoxic microenvironment was explored around the silencing information regulatory factor 1(SIRT1)/nuclear factor erythroid cell line 2 related factor 2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway. 50 SD rats were randomly divided into normal group, sham operation group, model group, Tongxinshu group, and positive drug group, with 10 rats in each group. The model group, Tongxinshu group, and positive drug group were treated with left anterior descending coronary artery ligation, and corresponding drugs were administered orally for 28 days after surgery. The effects of Tongxinshu Capsules on acute ischemic heart function were investigated through myocardial enzymes and cardiac body mass index. Masson staining and TTC staining observed the pathological changes and infarct size of myocardial infarction slices. The indexes were determined by enzyme linked immunosorbent assay(ELISA) to observe the relevant indicators of oxidative stress and iron homeostasis, this study comprehensively evaluates the effect of Tongxinshu Capsules on the microenvironment of the infarct margin in rats with myocardial infarction. Western blot detected protein levels of SIRT1 and its downstream signaling pathways Nrf2, HO-1, and SOD2. The results showed that compared with model group, Tongxinshu group reduced myocardial enzyme indicators such as LDH, CK-MB, and AST, and decreased the heart weight ratio. Masson staining showed the deposition of myocardial collagen fibers in Tongxinshu group was reduced. TTC staining showed a reduction in myocardial infarction area. Compared with model group, Tongxinshu group can reduce serum MDA, increase the levels of antioxidant stress markers such as GSH, GSH-Px, SOD2 in serum, and increase SOD2 content in cardiac tissue. Tongxinshu group can reduce the number of iron in cardiac tissue, and Prussian blue staining shows that it can reduce iron deposition in cardiac tissue of myocardial infarction rats, regulating the iron homeostasis balance of myocardial tissue after myocardial infarction. Compared with model group, Tongxinshu group activated the SIRT1 signaling pathway, and increased SIRT1, HO-1, and SOD2. The results indicate that Tongxinshu Capsules regulate energy metabolism remodeling through SIRT1/Nrf2/HO-1 signaling pathway, including improving the myocardial ischemia and hypoxia microenvironment. In summary, Tongxinshu Capsules can protect the cardiac function of rats with acute myocardial infarction, improve the microenvironmental disorders of oxidative stress and iron homeostasis, and its improvement of myocardial energy metabolism remodeling may be achieved through SIRT1/Nrf2/HO-1 signaling pathway.
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