Histone deacetylase inhibitor attenuates intestinal mucosal injury in fatally scalded rats

Rui Liu; Shu-Ming Wang; Si-Jia Guo; Ming-Ming Ma; Yi-Li Fu

doi:10.21037/atm-21-5766

Histone deacetylase inhibitor attenuates intestinal mucosal injury in fatally scalded rats

Ann Transl Med. 2022 Jan;10(2):54. doi: 10.21037/atm-21-5766.

Authors

Rui Liu^#^{1

2}, Shu-Ming Wang^#³, Si-Jia Guo², Ming-Ming Ma², Yi-Li Fu¹

Affiliations

¹ Center for Life Sciences, School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
² Department of Burns, Heilongjiang Provincial Hospital, Harbin, China.
³ Department of Emergency Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China.

^# Contributed equally.

Abstract

Background: Severe burns, trauma and shock can cause intestinal epithelial barrier dysfunction, which can lead to intestinal endotoxemia and even sepsis and multi-organ dysfunction. Many studies have shown that histone deacetylase inhibitors (HDACIs) can improve cell tolerance to hypoxia and inflammation, thus protecting the functions of important organs in the body, and at the same time, inhibiting the degradation of tight junction (TJ) proteins, protecting the intercellular barrier, and reducing tissue edema and organ damage. However, the mechanism is unclear.

Methods: Eighty male Sprague-Dawley rats (weighing 280-300 g) with a 50% total body surface area full-thickness dermal burn were randomly assigned to 4 groups (20 rats/group): sham control (SC group), scald + normal saline (SN group), scald + 2-methyl-2pentenoic acid (2M2P group), and scald + valproic acid (VPA group). After scalding, we measured the following parameters at various time intervals postburn injury: intestinal mucosal injury score, diamine oxidase (DAO) activity, intestinal protein expression of acetyl histone H3 at K9 (Ac-H3K9), hypoxia inducible factor 1α (HIF-1α), erythropoietin (EPO), zonula occludens-1 (ZO-1), endothelial nitric oxide synthase (eNOS) content, nitric oxide (NO) content, and intestinal mucosal blood flow (IMBF).

Results: Intestinal mucosa showed significant morphologic injury at 4 and 8 hours after scalding that was attenuated by VPA. DAO activity in the VPA group was significantly decreased compared with the other scald groups. At 4 and 8 hours after scalding, VPA enhanced Ac-H3K9 and ZO-1 expression and decreased HIF-1α and EPO expression in the intestine compared with the other scald groups. At 4 and 8 hours after scalding, eNOS and NO protein content and IMBF in the VPA group were markedly increased compared with the other scald groups.

Conclusions: HDACIs attenuated intestinal mucosal injury in fatally scalded rats. This may have involved VPA enhancing Ac-H3K9 and ZO-1 expression, inhibiting HIF-1α and EPO expression and inducing eNOS and NO increments.

Keywords: Burns; histone deacetylase inhibitor (HDACI); hypoxia inducible factor 1α (HIF-1α); valproic acid (VPA); zonula occludens-1 (ZO-1).