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Sodium Butyrate Ameliorates Intestinal Injury and Improves Survival in a Rat Model of Cecal Ligation and Puncture-Induced Sepsis

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Abstract

Sepsis is a life-threatening condition with a high rate of mortality. Unfortunately, very few therapies can improve outcomes in patients with sepsis. Butyrate, which is the most potent histone deacetylase (HDAC) inhibitor among short-chain fatty acids, exerts anti-inflammatory effects in a variety of inflammatory diseases. Butyrate might thus be valuable in the treatment of sepsis, in which inhibition of overwhelming cytokine release is vitally important. Sepsis was induced in 7- to 8-week-old Sprague-Dawley rats by cecal ligation and puncture (CLP) with a 21-g double-puncture technique. Rats received an intravenous injection of normal saline (vehicle) or sodium butyrate (200 mg/kg) after CLP and were sacrificed 12 h later. Hematoxylin and eosin staining was performed to observe the intestinal mucosal morphology. RT-PCR and ELISA were used to determine the intestinal inflammatory response in vivo. Intestinal permeability was evaluated by measuring fluorescein isothiocyanate dextran (FD-4) absorption in vivo, and tight junction protein expression was examined by western blot. NF-κB p65 activities were assessed by western blot and immunohistochemistry. Sodium butyrate treatment improved the survival rate of CLP rats and alleviated sepsis-induced intestinal mucosal injury. Proinflammatory cytokine expression was lower in butyrate-treated rats than in the vehicle group. FD-4 leakage from the intestinal tract was reduced, and the expression levels of the tight junction proteins claudin-1 and ZO-1 were also restored in rats that received sodium butyrate treatment. These effects were associated with less NF-κB p65 nuclear translocation, whereas the expression of Iκ-Bα was not affected or even increased. Sodium butyrate mitigates the inflammatory response and maintains intestinal barrier function in polymicrobial sepsis partly through inhibition of NF-κB activation and may serve as a novel therapy for sepsis.

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Abbreviations

CLP:

Cecal ligation and puncture

NaB:

Sodium butyrate

NF-κB:

Nuclear factor-kappa B

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Authors and Affiliations

  1. Department of Critical Care Medicine, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, 110004, Liaoning Province, China

    Jiahong Fu, Guofu Li, Xingmao Wu & Bin Zang

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  1. Jiahong Fu
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Fu, J., Li, G., Wu, X. et al. Sodium Butyrate Ameliorates Intestinal Injury and Improves Survival in a Rat Model of Cecal Ligation and Puncture-Induced Sepsis. Inflammation 42, 1276–1286 (2019). https://doi.org/10.1007/s10753-019-00987-2

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