Abstract
Effective drug intervention is the most important method to improve the prognosis, improve the quality of life, and prolong the life of patients with heart failure. This study aimed to explore the protective effect of astragaloside IV on myocardial cell injury induced by oxidized low-density lipoprotein (OxLDL) and its regulatory mechanism on the increase of brain natriuretic peptide (BNP) caused by myocardial cell injury. The model of myocardial cell injury, protection, and histone deacetylase (HDAC) inhibition in HL-1 mice was established by OxLDL treatment, astragaloside IV intervention, and UF010 coincubation. The effects of OxLDL and astragaloside IV on apoptosis were detected by flow cytometry. The expression level of BNP mRNA and protein in cells was investigated by real-time fluorescence quantification, western blot, and enzyme-linked immunosorbent assay. HDAC activity in nucleus was calibrated by fluorescence absorption intensity. Enzyme-linked immunosorbent assay (ELISA) was applied to test eNOS level in myocardial cells. OxLDL significantly promoted apoptosis, upregulated BNP mRNA, increased BNP protein level inside and outside cells, and decreased eNOS level. Compared with OxLDL treatment group, apoptosis decreased, BNP mRNA expression level decreased, BNP protein concentration decreased, and eNOS level increased significantly combined with low and high concentration astragaloside IV treatment group. HDAC activity significantly increased in OxLDL treatment group and significantly decreased after combined incubation with low and high concentrations of astragaloside IV. Inhibition of HDAC significantly increased eNOS level and decreased BNP protein level. In conclusion, astragaloside IV can reverse the low level of eNOS caused by OxLDL by regulating HDAC activity to protect myocardial cells from oxide damage, which is manifested by the decrease of BNP concentration.
Highlights
European Society of Cardiology [1, 2] has confirmed that heart failure has become one of the most common diseases in the world in the twenty-first century
Compared with oxidized low-density lipoprotein (OxLDL) treatment group, the apoptosis in the combined use of astragaloside IV group was significantly declined, and the role of high concentration astragaloside IV group was more obvious than that of lowconcentration group (P < 0.001). ere was no significant difference between the high-concentration group and blank control group (P > 0.05). e results of flow cytometric analysis of HL-1 cardiomyocyte apoptosis indicated that OxLDL can stably induce myocardial cell injury, and astragaloside IV can reduce OxLDL injury in a dose-dependent manner within a certain concentration range (Figure 1)
In order to explore the mechanism of astragaloside IV protecting myocardial cells from OxLDL injury, we quantitatively explored the protein activity of histone deacetylase (HDAC) by using enzyme activity detection kit. e fluorescence results showed that OxLDL significantly increased HDAC activity in HL-1 cells (q 16.72, P < 0.001), while both low and high concentrations of astragaloside IV significantly decreased HDAC activity induced by OxLDL (q1 17.23, q2 30.31, all P < 0.001) in a dose-dependent manner. ere was no significant difference in HDAC activity between high-concentration astragaloside group and blank control group (q 3.64, P 0.085) (Figure 4)
Summary
European Society of Cardiology [1, 2] has confirmed that heart failure has become one of the most common diseases in the world in the twenty-first century It is characterized by complicated diagnosis, difficulty in prevention, lack of treatment, and many complications. Journal of Healthcare Engineering regulation [8], macrophages and inflammatory factors [9, 10], and enzymology [11, 12] It has become a focus and hot spot to explore the pathogenesis from multiple angles and find effective drug intervention. E heart secretes natriuretic peptide, which is composed of 21–35 amino acid residues It can promote sodium excretion and urination, reduce the reabsorption of sodium by proximal convoluted tubules, and inhibit the release of aldosterone and plasma antidiuretic hormone. Clinical evaluation of its level (for the middle region of B-type natriuretic peptide (BNP), N-terminal proBNP, and N-terminal atrial natriuretic peptide) has become a valuable tool for diagnosing patients with heart failure and risk stratification [13, 14]
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