Activation of Opioid Receptors Attenuates Ischemia/Reperfusion Injury in Skeletal Muscle Induced by Tourniquet Placement
Background and Objectives. Tourniquet-induced ischemia/reperfusion (I/R) injury is a common clinical problem for patients receiving surgery. The objective of this study is to determine if oxycodone (Oxy) reduces skeletal muscle I/R damage induced by tourniquet placement and explores the underlying m...
Saved in:
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2021-01-01
|
Series: | Mediators of Inflammation |
Online Access: | http://dx.doi.org/10.1155/2021/6699499 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
_version_ | 1832555223558651904 |
---|---|
author | Yue-Xian Guo Gui-Ying Wang Wen-jie Cheng Cai-Zhen Yan Shuang Zhao Zhao Li Peng Liu Xiu-Li Wang |
author_facet | Yue-Xian Guo Gui-Ying Wang Wen-jie Cheng Cai-Zhen Yan Shuang Zhao Zhao Li Peng Liu Xiu-Li Wang |
author_sort | Yue-Xian Guo |
collection | DOAJ |
description | Background and Objectives. Tourniquet-induced ischemia/reperfusion (I/R) injury is a common clinical problem for patients receiving surgery. The objective of this study is to determine if oxycodone (Oxy) reduces skeletal muscle I/R damage induced by tourniquet placement and explores the underlying mechanisms. Method. Mice were randomly assigned to the sham, I/R, Oxy, and I/R with Oxy groups. Oxy was injected intraperitoneally 30 min before tourniquet placement. Morphological changes of the gastrocnemius muscle in these mice were assessed by hematoxylin-eosin (HE) staining and electron microscopy. Expression levels of TLR4, NF-κB, SIRT1, and PGC-1α in the skeletal muscles were detected by western blot. Blood TNF-α levels, gastrocnemius muscle contractile force, and ATP concentration were examined. Results. Compared with the I/R group, Oxy pretreatment attenuated skeletal muscle damage, decreased serum TNF-α levels, and inhibited the expression levels of TLR4/NF-κB in the gastrocnemius muscle. Furthermore, Oxy treatment significantly increased serum ATP levels and the contractility of the skeletal muscles. SIRT1 and PGC-1α levels were significantly reduced in gastrocnemius muscle after I/R. Oxy pretreatment recovered these protein expression levels. Conclusion. Tourniquet-induced acute limb I/R results in morphological and functional impairment in skeletal muscle. Pretreatment with Oxy attenuates skeletal muscle from acute I/R injury through inhibition of TLR4/NF-κB-dependent inflammatory response and protects SIRT1/PGC-1α-dependent mitochondrial function. |
format | Article |
id | doaj-art-54ec4d8e3086491892ae266a7c1c182c |
institution | Kabale University |
issn | 0962-9351 1466-1861 |
language | English |
publishDate | 2021-01-01 |
publisher | Wiley |
record_format | Article |
series | Mediators of Inflammation |
spelling | doaj-art-54ec4d8e3086491892ae266a7c1c182c2025-02-03T05:49:18ZengWileyMediators of Inflammation0962-93511466-18612021-01-01202110.1155/2021/66994996699499Activation of Opioid Receptors Attenuates Ischemia/Reperfusion Injury in Skeletal Muscle Induced by Tourniquet PlacementYue-Xian Guo0Gui-Ying Wang1Wen-jie Cheng2Cai-Zhen Yan3Shuang Zhao4Zhao Li5Peng Liu6Xiu-Li Wang7Department of Surgery, Hebei Medical University Third Affiliated Hospital, Shijiazhuang, Hebei 050051, ChinaDepartment of Surgery, Hebei Medical University Third Affiliated Hospital, Shijiazhuang, Hebei 050051, ChinaDepartment of Anesthesiology, Hebei Medical University Third Affiliated Hospital, Shijiazhuang, Hebei 050051, ChinaDepartment of Pharmacology, Hebei Medical University, Shijiazhuang, ChinaDepartment of Anesthesiology, Hebei Medical University Third Affiliated Hospital, Shijiazhuang, Hebei 050051, ChinaDepartment of Anesthesiology, Hebei Medical University Third Affiliated Hospital, Shijiazhuang, Hebei 050051, ChinaDepartment of Anesthesiology, Hebei Medical University Third Affiliated Hospital, Shijiazhuang, Hebei 050051, ChinaDepartment of Anesthesiology, Hebei Medical University Third Affiliated Hospital, Shijiazhuang, Hebei 050051, ChinaBackground and Objectives. Tourniquet-induced ischemia/reperfusion (I/R) injury is a common clinical problem for patients receiving surgery. The objective of this study is to determine if oxycodone (Oxy) reduces skeletal muscle I/R damage induced by tourniquet placement and explores the underlying mechanisms. Method. Mice were randomly assigned to the sham, I/R, Oxy, and I/R with Oxy groups. Oxy was injected intraperitoneally 30 min before tourniquet placement. Morphological changes of the gastrocnemius muscle in these mice were assessed by hematoxylin-eosin (HE) staining and electron microscopy. Expression levels of TLR4, NF-κB, SIRT1, and PGC-1α in the skeletal muscles were detected by western blot. Blood TNF-α levels, gastrocnemius muscle contractile force, and ATP concentration were examined. Results. Compared with the I/R group, Oxy pretreatment attenuated skeletal muscle damage, decreased serum TNF-α levels, and inhibited the expression levels of TLR4/NF-κB in the gastrocnemius muscle. Furthermore, Oxy treatment significantly increased serum ATP levels and the contractility of the skeletal muscles. SIRT1 and PGC-1α levels were significantly reduced in gastrocnemius muscle after I/R. Oxy pretreatment recovered these protein expression levels. Conclusion. Tourniquet-induced acute limb I/R results in morphological and functional impairment in skeletal muscle. Pretreatment with Oxy attenuates skeletal muscle from acute I/R injury through inhibition of TLR4/NF-κB-dependent inflammatory response and protects SIRT1/PGC-1α-dependent mitochondrial function.http://dx.doi.org/10.1155/2021/6699499 |
spellingShingle | Yue-Xian Guo Gui-Ying Wang Wen-jie Cheng Cai-Zhen Yan Shuang Zhao Zhao Li Peng Liu Xiu-Li Wang Activation of Opioid Receptors Attenuates Ischemia/Reperfusion Injury in Skeletal Muscle Induced by Tourniquet Placement Mediators of Inflammation |
title | Activation of Opioid Receptors Attenuates Ischemia/Reperfusion Injury in Skeletal Muscle Induced by Tourniquet Placement |
title_full | Activation of Opioid Receptors Attenuates Ischemia/Reperfusion Injury in Skeletal Muscle Induced by Tourniquet Placement |
title_fullStr | Activation of Opioid Receptors Attenuates Ischemia/Reperfusion Injury in Skeletal Muscle Induced by Tourniquet Placement |
title_full_unstemmed | Activation of Opioid Receptors Attenuates Ischemia/Reperfusion Injury in Skeletal Muscle Induced by Tourniquet Placement |
title_short | Activation of Opioid Receptors Attenuates Ischemia/Reperfusion Injury in Skeletal Muscle Induced by Tourniquet Placement |
title_sort | activation of opioid receptors attenuates ischemia reperfusion injury in skeletal muscle induced by tourniquet placement |
url | http://dx.doi.org/10.1155/2021/6699499 |
work_keys_str_mv | AT yuexianguo activationofopioidreceptorsattenuatesischemiareperfusioninjuryinskeletalmuscleinducedbytourniquetplacement AT guiyingwang activationofopioidreceptorsattenuatesischemiareperfusioninjuryinskeletalmuscleinducedbytourniquetplacement AT wenjiecheng activationofopioidreceptorsattenuatesischemiareperfusioninjuryinskeletalmuscleinducedbytourniquetplacement AT caizhenyan activationofopioidreceptorsattenuatesischemiareperfusioninjuryinskeletalmuscleinducedbytourniquetplacement AT shuangzhao activationofopioidreceptorsattenuatesischemiareperfusioninjuryinskeletalmuscleinducedbytourniquetplacement AT zhaoli activationofopioidreceptorsattenuatesischemiareperfusioninjuryinskeletalmuscleinducedbytourniquetplacement AT pengliu activationofopioidreceptorsattenuatesischemiareperfusioninjuryinskeletalmuscleinducedbytourniquetplacement AT xiuliwang activationofopioidreceptorsattenuatesischemiareperfusioninjuryinskeletalmuscleinducedbytourniquetplacement |