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Optimal intervention time of ADSCs for hepatic ischemia-reperfusion combined with partial resection injury in rats.
- Source :
-
Life sciences [Life Sci] 2021 Nov 15; Vol. 285, pp. 119986. Date of Electronic Publication: 2021 Sep 27. - Publication Year :
- 2021
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Abstract
- Aims: Hepatic ischemia reperfusion injury (HIRI) is a complication of liver surgery and liver transplantation. Adipose-derived stem cells (ADSCs) can inhibit oxidative stress and inflammation through a paracrine effect. This study aimed to determine the optimal time window of ADSCs transplantation to restore liver function after HIRI.<br />Main Methods: A rat model of hepatic ischemia reperfusion combined with partial hepatectomy (HIR/PH) was established. The animals were injected intravenously with 2 × 10 <superscript>6</superscript> rat ADSCs 2 h before, immediately after, or 6 h after surgery. Liver tissues and blood samples were collected for routine histological and biochemical assays. The molecular changes were analyzed by qRT-PCR and western blotting.<br />Key Findings: ADSCs significantly improved liver tissue structure and decreased the levels of AST, ALT and ALP, which was indicative of functional recovery. In addition, transplantation of ADSCs immediately after operation decreased the levels of inflammation-related cytokines such as TNF-α, IL-1β and IL-6, and significantly increased the activity of antioxidant enzymes. At the same time, the expression of MDA was decreased. Mechanistically, ADSCs activated the Keap1/Nrf2 pathway in the injured liver. Transplantation of ADSCs pre- and 6 h post-operation did not significantly affect some indices such as mRNA and protein expression of HO-1, and protein expression of NQO1.<br />Significance: Transplanting ADSCs immediately after surgery accelerated tissue repair and functional recovery of the liver by activating the Keap1/Nrf2 pathway, which inhibited hepatic inflammation and oxidative stress, and restored the hepatic microenvironment.<br /> (Copyright © 2021. Published by Elsevier Inc.)
- Subjects :
- Adipose Tissue cytology
Alanine Transaminase metabolism
Animals
Disease Models, Animal
Kelch-Like ECH-Associated Protein 1 metabolism
Liver enzymology
Male
NF-E2-Related Factor 2 metabolism
Phosphodiesterase I metabolism
Rats
Rats, Sprague-Dawley
Transaminases metabolism
Hepatectomy adverse effects
Liver blood supply
Liver surgery
Liver Regeneration
Liver Transplantation adverse effects
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells physiology
Reperfusion Injury etiology
Reperfusion Injury surgery
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0631
- Volume :
- 285
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 34592233
- Full Text :
- https://doi.org/10.1016/j.lfs.2021.119986