Dexmedetomidine Facilitates Liver Regeneration in Cirrhotic Mice after Partial Hepatectomy via the TLR4/NF-κB/IL-6 Pathway

Jia Wang, Dan Li, Huifang Zhang, Junfeng Li, Wenhong Liu, Su Mao, Qinfei Li, Jiang Qian

Article ID: 7061
Vol 37, Issue 1, 2023
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20233701.13
Received: 8 February 2023; Accepted: 8 February 2023; Available online: 8 February 2023; Issue release: 8 February 2023

Abstract

Objectives: This study investigates how Dexmedetomidine (Dex) impacts liver regeneration after partial hepatectomy (Hep) for cirrhosis. Methods: Cirrhosis was induced in mice via intraperitoneal injection with CCl4. Eight weeks after cirrhosis induction, intraperitoneal injection with Dex was initiated, 30 min before 50% partial Hep. The plasma levels of Bilirubin, alanine transaminase (ALT) and aspartate transaminase (AST) were measured by an automatic biochemical analyzer. The survival rate of cirrhotic mice was presented using Kaplan–Meier’s curve. Histopathological changes in the liver were examined by hematoxylin-eosin staining. Primary hepatocytes were isolated from the livers of cirrhotic mice with Dex treatment and Hep, and verified by Periodic Acid-Schiff staining. Primary hepatocyte proliferation was evaluated by CCK-8, colony formation, and immunofluorescence assays. The levels of IL-6, VEGF, STAT3, TLR4, TNF-α, NF-κB, CyclinD1, and Bcl-2 in the liver or the primary hepatocytes were analyzed by Western blot. Results: Dex reversed the effects of Hep on increasing levels of Bilirubin, ALT and AST, decreasing mouse weight, liver weight, the ratios of liver weight to mouse weight and survival rate, and aggravating cirrhosis and liver histopathological abnormalities in cirrhotic livers. Meanwhile, Dex further potentiated the effects of Hep on promoting hepatocyte proliferation, and the expression of IL-6, VEGF, STAT3, TLR4, NF-κB, CyclinD1 and Bcl-2 in cirrhotic livers. Primary hepatocytes were successfully isolated and characterized. TAK-242 (TLR4 inhibitor) inhibited the proliferation of these isolated hepatocytes and the expression of IL-6, TNF-α, TLR4 and NF-κB. Conclusions: Dex facilitates liver regeneration in cirrhotic mice after Hep probably via activating the TLR4/NF-κB/IL-6 pathway.


Keywords

dexmedetomidine;cirrhosis;liver regeneration;hepatocyte proliferation;the TLR4/NF-κB/IL-6 pathway


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