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Sodium Butyrate Reduces Organ Injuries in Mice with Severe Acute Pancreatitis Through Inhibiting HMGB1 Expression

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Abstract

Objective

The present study was designed to evaluate the effect of sodium butyrate on pancreas damage and to investigate the role of high-mobility group box-1 (HMGB1) and nuclear factor-κB (NF-κB) in the development of severe acute pancreatitis (SAP) in a mouse model.

Methods

The SAP model was established by intraperitoneal injection of two doses of 20 % L-2 arginine (200 mg/g). Female Sprague–Dawley mice were randomly allocated into three groups (n = 48/group): the control, untreated SAP, and sodium butyrate-treated SAP groups. The animals were euthanized at 0, 12, 24, and 48 h after the establishment of the SAP. Histopathology of the pancreas was performed, and the NF-κB levels were determined by immunohistochemistry. The serum levels of tumor necrosis factor (TNFα), interleukin-6 (IL-6), and HMGB1 were measured by ELISA. The HMGB1 mRNA levels were determined by qRT-PCR.

Results

The sodium butyrate-treated SAP animals showed significantly improved pancreas histopathology and lower serum amylase levels than the untreated SAP animals. In the SAP group, the mRNA levels of HMGB1 were remarkably increased at the 12 h, peaked at 24 h, and remained at a high level up to 48 h after L-2 arginine injection. The levels of TNFα and IL-6 were decreased at 48 h. Treatment with sodium butyrate reduced the pathological lesions, the serum levels of HMGB1, TNFα, and IL-6, the HMGB1 mRNA levels, and NF-κB activity.

Conclusion

Sodium butyrate inhibits the NF-κB activation and reduces pancreas injury in SAP through the modulation of HMGB1 and other inflammatory cytokine responses.

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Conflict of interest

The authors claim no conflicts of interest regarding the study or publication of this report.

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Authors and Affiliations

  1. Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, 214023, Jiangsu, People’s Republic of China

    Ting Zhang

  2. Wuxi People’s Hospital, No. 299 Qingyang Rd, Wuxi, 214023, Jiangsu, People’s Republic of China

    Min Xia, Qiang Zhan, Qunyan Zhou, Guomin Lu & Fangmei An

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  1. Ting Zhang
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  2. Min Xia
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  3. Qiang Zhan
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  4. Qunyan Zhou
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Correspondence to Min Xia.

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Zhang, T., Xia, M., Zhan, Q. et al. Sodium Butyrate Reduces Organ Injuries in Mice with Severe Acute Pancreatitis Through Inhibiting HMGB1 Expression. Dig Dis Sci 60, 1991–1999 (2015). https://doi.org/10.1007/s10620-015-3586-z

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  • DOI: https://doi.org/10.1007/s10620-015-3586-z

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