Dexmedetomidine facilitates autophagic flux to promote liver regeneration by suppressing GSK3ß activity in mouse partial hepatectomy.
Biomed Pharmacother
; 177: 117038, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-39002441
ABSTRACT
INTRODUCTION:
Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor agonist, is widely used for sedation and anesthesia in patients undergoing hepatectomy. However, the effect of DEX on autophagic flux and liver regeneration remains unclear.OBJECTIVES:
This study aimed to determine the role of DEX in hepatocyte autophagic flux and liver regeneration after PHx.METHODS:
In mice, DEX was intraperitoneally injected 5â¯min before and 6â¯h after PHx. In vitro, DEX was co-incubated with culture medium for 24â¯h. Autophagic flux was detected by LC3-II and SQSTM1 expression levels in primary mouse hepatocytes and the proportion of red puncta in AML-12 cells transfected with FUGW-PK-hLC3 plasmid. Liver regeneration was assessed by cyclinD1 expression, Edu incorporation, H&E staining, ki67 immunostaining and liver/body ratios. Bafilomycin A1, si-GSK3ß and Flag-tagged GSK3ß, α2-ADR antagonist, GSK3ß inhibitor, AKT inhibitor were used to identify the role of GSK3ß in DEX-mediated autophagic flux and hepatocyte proliferation.RESULTS:
Pre- and post-operative DEX treatment promoted liver regeneration after PHx, showing 12â¯h earlier than in DEX-untreated mice, accompanied by facilitated autophagic flux, which was completely abolished by bafilomycin A1 or α2-ADR antagonist. The suppression of GSK3ß activity by SB216763 and si-GSK3ß enhanced the effect of DEX on autophagic flux and liver regeneration, which was abolished by AKT inhibitor.CONCLUSION:
Pre- and post-operative administration of DEX facilitates autophagic flux, leading to enhanced liver regeneration after partial hepatectomy through suppression of GSK3ß activity in an α2-ADR-dependent manner.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autophagy
/
Dexmedetomidine
/
Hepatocytes
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Glycogen Synthase Kinase 3 beta
/
Hepatectomy
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Liver Regeneration
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Mice, Inbred C57BL
Limits:
Animals
Language:
En
Journal:
Biomed Pharmacother
Year:
2024
Document type:
Article