Search

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., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

It is known that the epigenetic process of histone acetylation is involved in the neuropathic pain. The aim of this study was to determine whether sirtuin type 1 (SIRT1), an NAD + dependent deacetylase, affected allodynia and hyperalgesia in neuropathic pain. The neuropathic pain model was established by ligature of the right sciatic nerve to induce chronic constriction injury (CCI) in rats. Histone acetyltransferase (HAT) activity was increased and, and histone deacetylase (HDAC) activity was declined in tissue of the spinal dorsa horn in CCI rates by means of enzyme-linked immunosorbent assay (ELISA). The persistent hyperalgesia and allodynia caused by CCI were associated with downregulation of SIRT1 and upregulation of acetylated-H3 (Ac-H3) in tissue of the spinal cord by Western blot assay, which was reversed after intrathecal injection of SIRT1 agonist SRT1720. SRT1720 treatment achieved analgesic through inhibiting the acetylation of nuclear factor kappa B (NF-κB) and blocking the releases of the inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 by means of Western blot and real-time quantitative PCR (RT-PCR), respectively. Taken together, these data suggest that SIRT1 in the spinal cord plays an important role in the neuropathic pain in the rat model., Competing Interests: None., (IJCEP Copyright © 2018.)