lancet-header
Preprints with The Lancet is part of SSRN´s First Look, a place where journals and other research experts identify content of interest prior to publication. These preprint papers are not peer-reviewed and are posted here as part of a 12-month trial. Authors have either opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet, or submitted directly via SSRN. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. These papers should not be used for clinical decision making or reporting of research to a lay audience without indicating that this is preliminary research that has not been peer-reviewed. For more information see the Comment published in The Lancet, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com

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

35 Pages Posted: 3 Jun 2019

See all articles by Xue-Kang Zhang

Xue-Kang Zhang

Nanchang University - Department of Anesthesiology

Xiao-Ming Liu

Nanchang University - First Affiliated Hospital

Qian Hu

Nanchang University - Department of Anesthesiology

Zheng-Ren Liu

Nanchang University - First Affiliated Hospital

Zhi-Yi Liu

Nanchang University - Department of Anesthesiology

Huai-Gen Zhang

Nanchang University - Department of Anesthesiology

Qin Zhang

Nanchang University - Department of Anesthesiology

Yuan-Lu Huang

Nanchang University - Department of Anesthesiology

Qiu-Hong Chen

Nanchang University - Department of Anesthesiology

Wen-Xiang Wang

Nanchang University - Department of Anesthesiology

More...

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.

Keywords: Dexmedetomidine; Intestinal ischemia-reperfusion; Enteric glial cells; Mitochondria translocation of telomerase reverse transcriptase; Oxidative stress

Suggested Citation

Zhang, Xue-Kang and Liu, Xiao-Ming and Hu, Qian and Liu, Zheng-Ren and Liu, Zhi-Yi and Zhang, Huai-Gen and Zhang, Qin and Huang, Yuan-Lu and Chen, Qiu-Hong and Wang, Wen-Xiang, Dexmedetomidine Rescues Enteric Glial Cells from Oxidative Stress-Induced Intestinal Ischemia-Reperfusion Injury Through Promoting Mitochondrial Translocation of Telomerase Reverse Transcriptase (May 31, 2019). Available at SSRN: https://ssrn.com/abstract=3397181

Xue-Kang Zhang (Contact Author)

Nanchang University - Department of Anesthesiology ( email )

Nanchang
China

Xiao-Ming Liu

Nanchang University - First Affiliated Hospital

999 Xuefu Avenue
Hong Gu Tan New District
Nanchang, Jiangxi 330031
China

Qian Hu

Nanchang University - Department of Anesthesiology

Nanchang
China

Zheng-Ren Liu

Nanchang University - First Affiliated Hospital

999 Xuefu Avenue
Hong Gu Tan New District
Nanchang, Jiangxi 330031
China

Zhi-Yi Liu

Nanchang University - Department of Anesthesiology

Nanchang
China

Huai-Gen Zhang

Nanchang University - Department of Anesthesiology

Nanchang
China

Qin Zhang

Nanchang University - Department of Anesthesiology

Nanchang
China

Yuan-Lu Huang

Nanchang University - Department of Anesthesiology

Nanchang
China

Qiu-Hong Chen

Nanchang University - Department of Anesthesiology

Nanchang
China

Wen-Xiang Wang

Nanchang University - Department of Anesthesiology

Nanchang
China

Click here to go to TheLancet.com

Go to TheLancet.com

Paper statistics

Abstract Views
31
Downloads
6