Astragaloside IV Reduces OxLDL-Induced BNP Overexpression by Regulating HDAC

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.

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Role of Thrombospondin-1 in Sepsis-Induced Myocardial Injury

10.21203/rs.3.rs-395547/v1 ◽

2021 ◽

Author(s):

YUN XIE ◽

JIAXIANG ZHANG ◽

WEI JIN ◽

RUI TIAN ◽

Ruilan Wang

Keyword(s):

Mrna Expression ◽

Real Time ◽

Quantitative Pcr ◽

Myocardial Injury ◽

Cell Injury ◽

Myocardial Cell ◽

Expression Level ◽

Myocardial Cells ◽

Thrombospondin 1 ◽

Myocardial Cell Injury

Abstract Objective: Sepsis often causes myocardial injury with a high mortality. We wanted to investigate the effects of thrombospondin-1 (THBS1) expression on myocardial cell injury, oxidative stress and apoptosis in sepsis.Methods: The expression of THBS1 mRNA in LPS-induced mouse primary cardiomyocytes was detected by real-time fluorescence quantitative PCR. We constructed a eukaryotic siRNA expression vector and used liposome transfection to knockdown THBS1 mRNA expression in myocardial cells. We detected the THBS1 mRNA expression level using real-time fluorescent quantitative PCR. Four groups were used: control, LPS, THBS1 siRNA, and LPS + THBS1 siRNA. ELISA was used to detect cTnI, proBNP, ROS, caspase3 and other indicators of cell damage. At the same time, sepsis mouse models were prepared for H&E, TUNEL and caspase-3 staining to evaluate myocardial cell injury and apoptosis. Clinical samples were collected to analyze the serum THBS1 level and correlate it with the prognosis of patients with myocardial injury of sepsis.Results: The expression level of THBS1 mRNA in myocardial cells induced by LPS was increased, and the serum THBS1 level in patients with myocardial injury in sepsis was also significantly increased. In the THBS1 siRNA group with myocardial injury, the levels of cTnI and proBNP were significantly decreased, the levels of the inflammatory cytokines IL-6 and TNF-α were significantly decreased, ROS were significantly decreased, and caspase3 was significantly decreased, and myocardial cell apoptosis was also reduced in the sepsis mouse model. Conclusion: THBS1 is closely related to the biological behavior of myocardial cells and may be a therapeutic target for myocardial injury in sepsis.

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