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Astragaloside IV Attenuates Polymicrobial Sepsis-Induced Cardiac Dysfunction in Rats via IKK/NF-κB Pathway

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Abstract

Objective

To evaluate the protective effects of Astragaloside IV (AST) in a rat model of myocardial injury induced by cecal ligation and puncture (CLP).

Methods

The model of sepsis-induced cardiac dysfunction was induced by CLP. Using a random number table, 50 specific pathogen free grade of Sprague Dawley rats were randomized into 5 groups: the sham group (sham), the model group (CLP, 18 h/72 h) and AST group (18 h/72 h). Except the sham group, the rats in other groups received CLP surgery to induce sepsis. CLP groups received intragastric administration with normal saline after CLP. AST groups received intragastric administration with AST solution (40 mg/kg) once a day. The levels of inflammatory mediators and oxidative stress markers in the serum of the septic rats were determined via enzyme-linked immunosorbent assay (ELISA) at different time point, such as interleukin 6 (IL-6), IL-10, high mobility group box-1 protein B1 (HMGB-1), superoxide dismutase (SOD), and malondialdehyde (MDA). Cardiac function was determined by echocardiography. Moreover, changes in myocardial pathology were evaluated using hematoxylin and eosin staining. The levels of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) were analysed to determine the status of CLP-induced myocardium. In addition, the apotosis of myocardial cells was analysed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). The protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), IκB kinase α (IKKα), nuclear factor kappa B p65 (NF-κB p65) were detected by Western blot analysis. Moreover, survival rate was investigated.

Results

AST improved the survival rate of CLP-induced rats by up to 33.3% (P<0.05). The cardioprotective effect of AST was observed by increased ejection fraction, fractional shortening and left ventricular internal diameter in diastole respectively (P<0.01 or P<0.05). Subsequently, AST attenuated CLP-induced myocardial apoptosis and the ratio of Bcl-2/Bax in the myocardium, as well as the histological alterations of myocardium (P<0.01 or P<0.05); the generation of inflammatory cytokines (IL-6, IL-10, HMGB-1) and oxidative stress markers (SOD, MDA) in the serum was significantly alleviated (P<0.01 or P<0.05). On the other hand, AST markedly suppressed CLP-induced accumulation of IKK-α and NF-κB p65 subunit phosphorylation (P<0.01 or P<0.05).

Conclusions

AST plays a significant protective role in sepsis-induced cardiac dysfunction and survival outcome. The possible mechanism of cardioprotection is dependent on the activation of the IKK/NF-κB pathway in cardiomyocytes.

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Authors and Affiliations

  1. Intensive Care Research Team of Traditional Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, the Second Clinical Collage of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China

    Xin Huang & Shi-yu Ma

  2. Department of Critical Care Medicine, Guangdong Provincial Hospital of Chinese Medicine, the Second Clinical Collage of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China

    Min-zhou Zhang, Xin Yin & Li-heng Guo

  3. Department of Radiology, Guangdong Provincial Hospital of Chinese Medicine, the Second Clinical Collage of Guangzhou University of Chinese Medicine, Guangzhou, 510120, China

    Bo Liu

Authors
  1. Xin Huang
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  2. Min-zhou Zhang
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  4. Shi-yu Ma
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  5. Xin Yin
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Contributions

Huang X performed the experiments and wrote the manuscript. Guo LH designed the study, Yin X and Ma SY contributed some experiments and the data analysis. Zhang MZ and Liu B revised the manuscript.

Corresponding author

Correspondence to Li-heng Guo.

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The authors declare no conflicts of interest.

Additional information

Supported by Science and Technology Department of Guangdong Province (No. 2014A020212277) and Specific Science and Technology Research Fund of Guangdong Province (No. YN2015QN07)

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Huang, X., Zhang, Mz., Liu, B. et al. Astragaloside IV Attenuates Polymicrobial Sepsis-Induced Cardiac Dysfunction in Rats via IKK/NF-κB Pathway. Chin. J. Integr. Med. 27, 825–831 (2021). https://doi.org/10.1007/s11655-021-2869-9

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