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SS31 Ameliorates Sepsis-Induced Heart Injury by Inhibiting Oxidative Stress and Inflammation

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Abstract

Sepsis-induced myocardial dysfunction (SIMD), lack of effective treatment, accounts for high mortality of sepsis. Mitochondrion-targeted antioxidant peptide SS31 has been revealed to be responsible for certain cardiovascular disease by ameliorating oxidative stress injury. But whether it protects a septic heart remains little known. This study sought to prove that SS31 was capable of improving sepsis-induced myocardial dysfunction dramatically. C57BL/6 mice were intraperitoneally administered lipopolysaccharide (LPS), exposed to systemic inflammation. Thirty-five C57BL/6 mice were randomly divided into four groups: sham group, LPS group (5 mg/kg), SS31 group (5 mg/kg), and SS31 + LPS group (treatment group). Heart tissues were harvested for pathological examination at the indicated time points. H9C2 cell were treated with LPS with or without the presence of SS31 (10 μM) at 37 °C to assess the effect on cardiomyocytes at the indicated time points. SS31 restored myocardial morphological damage and suppressed inflammatory response as evidenced by significantly decreasing the mRNA levels of IL-6, IL-1β, and TNF-α in vitro and in vivo. In addition, myocardial energy deficiency secondary to sepsis was remarkedly ameliorated by SS31. Furthermore, we found that SS-31 normalized the activity of malondialdehyde, glutathione peroxidase, and superoxide dismutase in vitro and in vivo, and maintained mitochondrial membrane potential (MMP) as well. And western blot was applied to measure the expressions of p-p38MAPK, p-JNK1/2, p-ERK, p62, and NF-κB p65; the results illuminated that the cardioprotective effect of SS31 was partly linked to NF-κB. In conclusion, SS31 therapy effectively protected the heart against LPS-induced cardiac damage.

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Funding

This investigation was supported by the grants from the Natural Science Foundation of Hubei Province of China (2017CFB674, 2018CFB701), Science and Technology Plan Project of Xiangyang (2014-7-16), the Innovative Team Project (2017-2019) from the Institute of Medicine and Nursing at Hubei University of Medicine, and the Initial Project for Ph.D of Hubei University of Medicine (2015QDJZR03).

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Author notes

  1. Yue Liu, Wenjian Yang, Xiaodong Sun, Lixia Xie, Yi Yang, Ming Sang and Rong Jiao contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics, Xiangyang No.1 People’s Hospital, Hubei University of Medicine, No. 15 Jiefang Road, Xiangyang, 441000, Hubei Province, People’s Republic of China

    Yue Liu, Wenjian Yang, Xiaodong Sun, Lixia Xie, Yi Yang, Ming Sang & Rong Jiao

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  1. Yue Liu
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Contributions

R.J., M.S., Y.L., and X.D.S. conceived and designed this study. Y.L. carried out experiments. W.J.Y., Y.Y., and L.X.X. collected and analyzed data. W.J.Y. performed statistical analysis. Y.L. and W.J.Y. wrote the manuscript, which was critically reviewed and revised by R.J. and M.S. All authors read and approved the final manuscript.

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Correspondence to Rong Jiao.

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And all the procedures were conducted in accordance with the Guidelines for the Care and Use of Laboratory Animals published by the United States National Institutes of Health (NIH Publication, revised 2011) and were approved by the Ethical Committee for Animal Experimentation of Xiangyang No.1 People’s Hospital.

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The authors declare that they have no conflict of interest.

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Supplementary Fig. 1.

Effects of SS31 on H9C2 cell viability. Cells were treated with different concentrations of SS31 (5, 10, 20, 40, and 80 μM) or LPS (3.125, 6.25, 12.5, 25, 50, 100 and 200 μM) for 12 h. Cell viability was measured and presented as mean ± SEM. H9C2 cells were seeded in 96-well plates, and the result of each concentration was the calculated mean of six wells. (PNG 36 kb)

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Supplementary Fig. 2.

SS31 and autophagy. The gene expression of beclin-1, p62, atg3 in heart tissues were estimated by RT-PCR at different time point after LPS or LPS + SS31. The values are expressed as means ± SEM (n = 8 per group). *P < 0.05 vs. control group; #P < 0.05 vs. LPS group. (PNG 72 kb)

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Liu, Y., Yang, W., Sun, X. et al. SS31 Ameliorates Sepsis-Induced Heart Injury by Inhibiting Oxidative Stress and Inflammation. Inflammation 42, 2170–2180 (2019). https://doi.org/10.1007/s10753-019-01081-3

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