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Cell Physiol Biochem. 2018;47(2):556-566. doi: 10.1159/000489989. Epub 2018 May 22.

Intravenous Anesthetics Enhance the Ability of Human Bone Marrow-Derived Mesenchymal Stem Cells to Alleviate Hepatic Ischemia-Reperfusion Injury in a Receptor-Dependent Manner.

Author information

1
Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
2
The First People's Hospital of Foshan, Affiliated FoShan Hospital of Sun Yat-sen University, Foshan, China.
3
Center for Stem Cell Biology and Tissue Engineering, Sun Yat-Sen University, Guangzhou, China.

Abstract

BACKGROUND/AIMS:

The degree of hepatic ischemia-reperfusion injury (HIRI) is highly relevant to the incidence of postoperative liver failure and mortality. Bone marrow-derived mesenchymal stem cells (BM-MSCs) have been shown to migrate to the liver and restore the damaged liver. Intravenous anesthetics are commonly used in the perioperative period; however, it is not yet known whether they have an influence on the functions of BM-MSCs and eventually affect the recovery of HIRI.

METHODS:

A rat model of HIRI and a hypoxia-reoxygenation (H/R) model using L02 cells were generated, and human BM-MSCs (hBM-MSCs) were injected through the portal vein or co-cultured with L02 cells in a Transwell system, respectively. Three intravenous anesthetics, namely, dexmedetomidine, midazolam, and propofol, were given as pretreatments to hBM-MSCs. Quantitative real-time PCR for growth factors (HGF, FGF, VEGF, and IGF) and a migration assay were used to detect the paracrine and migration abilities of hBM-MSCs. NF-κB expression was detected using an immunofluorescence method. Furthermore, three receptor inhibitors, namely, yohimbine, PK11195, and bicuculline, were given to explore whether the three anesthetics worked in a receptor-dependent manner.

RESULTS:

Preconditioning with dexmedetomidine and midazolam, but not propofol, enhanced the efficacy of hBM-MSCs in HIRI. Dexmedetomidine and midazolam, but not propofol, changed the paracrine spectrum and NF-κB p65 nuclear translocation of hBM-MSCs co-cultured with L02 cells after H/R injury. All three anesthetics enhanced the migration ability of hBM-MSCs when cultured in L02 H/R conditioned medium. However, the addition of receptor antagonists resulted in an opposite tendency.

CONCLUSIONS:

The intravenous anesthetics dexmedetomidine and midazolam enhanced the liver protective effects of hBM-MSCs during HIRI more effectively than propofol, by binding with their receptors and regulating the paracrine effect, migration ability, and NF-κB p65 nuclear translocation of hBM-MSCs.

KEYWORDS:

Hepatic ischemia-reperfusion injury; Human bone marrow-derived mesenchymal stem cells; Intravenous anesthetics; NF-κB

PMID:
29794450
DOI:
10.1159/000489989
[Indexed for MEDLINE]
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