Dexmedetomidine Rescues Enteric Glial Cells from Oxidative Stress-Induced Intestinal Ischemia-Reperfusion Injury Through Promoting Mitochondrial Translocation of Telomerase Reverse Transcriptase

Abstract

Background: Intestinal ischemia-reperfusion injury (IRI) is a devastating complication in the perioperative period leading to systemic inflammation and multiple organ dysfunction. We aimed to determine whether dexmedetomidine protects against oxidative stress injury induced by mitochondrial translocation of telomerase reverse transcriptase (TERT) in enteric glial cells (EGCs) of a rat model after intestinal IRI and the mechanisms involved in this protection. Methods: After the rat model with intestinal IRI was established, the rats were treated with high/low dose of dexmedetomidine. The positive rate of TERT protein was detected by immunohistochemistry. The distribution and levels of TERT were measured by immunofluorescence. The levels of apoptosis-related proteins and oxidative stress injury-related factors (ROS, MDA, and GSH) were also measured. Mitochondrial membrane permeability and potential were detected using Calcein cobalt and Rhodamine 123 staining respectively. The oxidative injury of mtDNA was detected by real-time fluorescence quantitative PCR. Cell Counting Kit-8 (CCK-8) assay and flow cytometry were applied to detection of EGC viability and apoptosis. Results: Relative to normal rats, rats with intestinal IRI displayed with reduced TERT mitochondrial translocation and EGC viability, as well as elevated mitochondrial damage, oxidative stress, and EGC apoptosis. Dexmedetomidine treatment could alleviate intestinal IRI by promoting mitochondrial translocation of TERT, reducing mitochondrial damage and oxidative stress. The regulatory mechanism functioned in a dose-dependent manner. Conclusion: Dexmedetomidine restores mitochondrial translocation of TERT, thus reducing oxidative stress and mitochondrial damage in EGCs after intestinal IRI. Funding: The study was supported by a grant from the National Natural Science Foundation of China (No. 81660096). Declaration of Interest: The authors have no competing interests to declare. Ethical Approval: Our study was approved by the Institutional Review Board of the First Affiliated Hospital of Nanchang University. All animal experiments and procedures were performed in accordance with the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health.