Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Sep 15, 2024; 15(9): 1962-1978
Published online Sep 15, 2024. doi: 10.4239/wjd.v15.i9.1962
Dexmedetomidine ameliorates diabetic intestinal injury by promoting the polarization of M2 macrophages through the MMP23B pathway
Man Lu, Xiao-Wen Guo, Fang-Fang Zhang, Dan-Hong Wu, Di Xie, Feng-Qin Luo
Man Lu, Xiao-Wen Guo, Fang-Fang Zhang, Dan-Hong Wu, Feng-Qin Luo, Department of Anesthesiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou 310006, Zhejiang Province, China
Di Xie, Department of Emergency, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Author contributions: Luo FQ designed the research study; Lu M, Guo XW, Zhang FF, and Wu DH performed the research; Xie D contributed new reagents and analytic tools; Lu M, Guo XW, Zhang FF, Wu DH, and Luo FQ analyzed the data and wrote the manuscript. All authors have read and approved the final manuscript.
Institutional animal care and use committee statement: This study was reviewed and approved by the Medical Ethics Committee of Xinhua Hospital, Shanghai Jiao Tong University School of Medicine (Approval No. XHEC-STCSM-2021-028).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Raw data can be obtained by contacting the corresponding author.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Feng-Qin Luo, MM, Attending Doctor, Department of Anesthesiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), No. 54 Youdian Lane, Shangcheng District, Hangzhou 310006, Zhejiang Province, China. 3021702500@qq.com
Received: June 5, 2024
Revised: July 17, 2024
Accepted: August 12, 2024
Published online: September 15, 2024
Processing time: 83 Days and 3.9 Hours
Abstract
BACKGROUND

Diabetes is often associated with gastrointestinal dysfunctions, which can lead to hypoglycemia. Dexmedetomidine (DEX) is a commonly used sedative in perioperative diabetic patients and may affect gastrointestinal function.

AIM

To investigate whether sedative doses of DEX alleviate diabetes-caused intestinal dysfunction.

METHODS

Sedation/anesthesia scores and vital signs of streptozotocin (STZ)-induced diabetic mice under DEX sedation were observed. Diabetic mice were divided into saline and DEX groups. After injecting sedatives intraperitoneally, tight junctions (TJs) and apoptotic levels were evaluated 24 hours later to assess the intestinal barrier function. The role of DEX was validated using Villin-MMP23B flox/flox mice with intestinal epithelial deletion. In vitro, high glucose and hyperosmolarity were used to culture Caco-2 monolayer cells with STZ inter-vention. Immunofluorescence techniques were used to monitor the barrier and mitochondrial functions.

RESULTS

MMP23B protein levels in the intestinal tissue of STZ-induced diabetic mice were significantly higher than those in the intestinal tissue of control mice, with the DEX group displaying decreased MMP23B levels. Diabetes-mediated TJ dis-ruption, increased intestinal mucosal permeability, and systemic inflammation in wild-type mice might be reversed by DEX. In Caco-2 cells, MMP23B was associated with increased reactive oxygen species accumulation, mitochondrial membrane potential depolarization, and TJ disruption.

CONCLUSION

DEX reduces MMP23B, which may potentially contribute to STZ-induced intestinal barrier dysfunction, affecting TJ modification through mitochondrial dysfunction.

Keywords: Diabetes; Dexmedetomidine; Intestinal barrier; Piezo1; Tight junctions

Core Tip: This study investigates the protective role of dexmedetomidine (DEX) in diabetic intestinal injury through the MMP23B pathway. The findings reveal that DEX acts as a sedative and enhances intestinal barrier function by promoting M2 macrophage polarization and reducing mitochondrial dysfunction. Streptozotocin-induced diabetic mice and Caco-2 cell models provide robust evidence of the potential therapeutic benefits of DEX, offering insights into its dual functionality in managing sedation and intestinal healing under diabetic conditions. This research can pave the way for the development of new treatment strategies targeting intestinal complications in diabetic patients.