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...

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Main Authors: Yue-Xian Guo, Gui-Ying Wang, Wen-jie Cheng, Cai-Zhen Yan, Shuang Zhao, Zhao Li, Peng Liu, Xiu-Li Wang
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2021/6699499
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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.
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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
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