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Intravenous immunoglobulin is effective in alleviating hepatic ischemia–reperfusion injury: a rat model study

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Abstract

Background

Hepatic ischemia–reperfusion injury (I/R) is an important factor affecting the prognosis of patients undergoing liver surgery. This study aimed to explore the value of intravenous immunoglobulin (IVIG) in hepatic I/R and its mechanism in a rat model.

Materials and methods

Forty eight adult male Sprague–Dawley (SD) rats were divided into six groups randomly: (1–2) treated with normal saline (NS) without ischemia or reperfusion; (3–4) treated with NS + 30 min ischemia; (5–6) treated with IVIG + 30 min ischemia. Rats of group 1/3/5 were euthanized at 12 h after operation (sham + NS + 12 h, I/R + NS + 12 h, I/R + IVIG + 12 h group) while group 2/4/6 were euthanized at 24 h (sham + NS + 24 h, I/R + NS + 24 h, I/R + IVIG + 24 h group). Interleukin 10 (IL-10), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) were quantified as well as serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Hepatic pathological changes were observed while nuclear factor kappa B p65 (NF-κB p65), Inhibitory Subunit of NF Kappa B Alpha (IKB-alpha) and cleaved caspase-3 were detected.

Conclusion

ALT, AST, IL-6, TNF-alpha, NF-κB p65 and cleaved caspase-3 were increased by I/R whereas IL-10 and IKB-alpha were decreased. However, IVIG pretreatment reduced ALT, AST, IL-6, TNF-alpha, NF-κB p65 and cleaved caspase-3, but increased IL-10 and IKB-alpha. IVIG treatment attenuates the infiltration of inflammatory cell and cell apoptosis which were observed in I/R groups. IVIG may alleviate hepatic I/R in rats by inhibiting the classical NF-κB signaling pathway, reducing IL-6, TNF-alpha, promoting IL-10, and inhibiting cell apoptosis.

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Abbreviations

ALT:

Glutamic pyruvic transaminase

AST:

Aspartate aminotransferase

IgG:

Immunoglobulin G

NS:

Normal saline

IL-6:

Interleukin 6

TNF-alpha:

Tumor necrosis factor-alpha

NF-κB:

P65 nuclear factor kappa B p65

IKB-alpha:

Inhibitory Subunit of NF Kappa B Alpha

IL-10:

Interleukin 10

IVIG:

Intravenous immunoglobulin

I/R:

Ischemia + reperfusion

MFI:

The mean fluorescence intensity

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Acknowledgements

This work was supported by the Medical Science and Technology Research Foundation of Guangdong province (Grant No. A2015513), and Shantou Medical and Health Science and Technology Project (Grant No. 190620235268989).

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Author notes

  1. Zeming Chen and Runzhui Lin have contributed equally to this work and are cofirst authors.

Authors and Affiliations

  1. Shantou University Medical College, Shantou, China

    Zeming Chen, Runzhui Lin, Hua Zhuo & Fengjie Xu

  2. Second Affiliated Hospital of Shantou University Medical College, Shantou, China

    Xingmu Liu

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  1. Zeming Chen
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  2. Runzhui Lin
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  3. Hua Zhuo
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  4. Fengjie Xu
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Contributions

ZC and RL designed and performed experiments, analyzed data and wrote the article. HZ and FX helped performing experiments. HZ and XL helped with preparation of the article. XL oversaw the design of the study, coordinated analyses, and revised the article.

Corresponding author

Correspondence to Xingmu Liu.

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Conflict of interest

The authors have no conflicts of interest to declare that are relevant to the content of this article.

Ethical approval

Animal experiments during our study were performed according to the guidelines for animal use provided by the Animal Experimental Center. Our experimental scheme was approved by the Animal Experimental Ethics Committee of Shantou University Medical College. And all applicable institutional and governmental regulations concerning the ethical use of animals were followed.

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Chen, Z., Lin, R., Zhuo, H. et al. Intravenous immunoglobulin is effective in alleviating hepatic ischemia–reperfusion injury: a rat model study. Mol Biol Rep 49, 341–349 (2022). https://doi.org/10.1007/s11033-021-06879-9

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