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阿片受体激动剂可减轻止血带引起的骨骼肌缺血/再灌注损伤。

Activation of Opioid Receptors Attenuates Ischemia/Reperfusion Injury in Skeletal Muscle Induced by Tourniquet Placement.

机构信息

Department of Surgery, Hebei Medical University Third Affiliated Hospital, Shijiazhuang, Hebei 050051, China.

Department of Anesthesiology, Hebei Medical University Third Affiliated Hospital, Shijiazhuang, Hebei 050051, China.

出版信息

Mediators Inflamm. 2021 Jan 15;2021:6699499. doi: 10.1155/2021/6699499. eCollection 2021.

DOI:10.1155/2021/6699499
PMID:33510583
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7822682/
Abstract

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-B, SIRT1, and PGC-1 in the skeletal muscles were detected by western blot. Blood TNF- 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- levels, and inhibited the expression levels of TLR4/NF-B in the gastrocnemius muscle. Furthermore, Oxy treatment significantly increased serum ATP levels and the contractility of the skeletal muscles. SIRT1 and PGC-1 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-B-dependent inflammatory response and protects SIRT1/PGC-1-dependent mitochondrial function.

摘要

方法

将小鼠随机分为假手术组、缺血再灌注组(I/R 组)、Oxy 组和缺血再灌注加 Oxy 组(I/R 加 Oxy 组)。Oxy 在止血带放置前 30min 经腹腔注射。通过苏木精-伊红(HE)染色和电子显微镜评估这些小鼠腓肠肌的形态变化。通过 Western blot 检测骨骼肌中 TLR4、NF-B、SIRT1 和 PGC-1 的表达水平。检测血清 TNF-水平、腓肠肌收缩力和 ATP 浓度。

结果

与 I/R 组相比,Oxy 预处理可减轻骨骼肌损伤,降低血清 TNF-水平,并抑制腓肠肌中 TLR4/NF-B 的表达水平。此外,Oxy 处理可显著增加血清 ATP 水平和骨骼肌的收缩力。I/R 后腓肠肌中 SIRT1 和 PGC-1 水平明显降低。Oxy 预处理可恢复这些蛋白的表达水平。

结论

止血带引起的急性肢体 I/R 导致骨骼肌的形态和功能损伤。Oxy 预处理可通过抑制 TLR4/NF-B 依赖性炎症反应来减轻骨骼肌的急性 I/R 损伤,并保护 SIRT1/PGC-1 依赖性线粒体功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eea/7822682/f761d501c17b/MI2021-6699499.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eea/7822682/c5f652be731b/MI2021-6699499.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eea/7822682/fc12c0cd09e0/MI2021-6699499.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eea/7822682/b3c77f9ab7b8/MI2021-6699499.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eea/7822682/b04e5734131d/MI2021-6699499.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eea/7822682/bde50ef6d676/MI2021-6699499.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eea/7822682/f761d501c17b/MI2021-6699499.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eea/7822682/c5f652be731b/MI2021-6699499.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eea/7822682/fc12c0cd09e0/MI2021-6699499.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eea/7822682/b3c77f9ab7b8/MI2021-6699499.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eea/7822682/b04e5734131d/MI2021-6699499.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eea/7822682/bde50ef6d676/MI2021-6699499.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7eea/7822682/f761d501c17b/MI2021-6699499.006.jpg

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