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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 15 - 2024 |
doi: 10.3389/fphar.2024.1453938
Dexmedetomidine regulates the anti-oxidation and autophagy of adipose-derived stromal cells under H2O2-induced oxidative stress through Nrf2/p62 pathway and improves the retention rate of autologous fat transplantation Authors and affiliations
Provisionally accepted- First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China
To investigate the protective mechanism of dexmedetomidine (DEX) on adipose-derived stromal cells (ADSCs) under oxidative stress model and its promotion effect on the retention rate of adipose granule transplantation by in vitro and in vivo experiments. The experiment was divided into control group, model group (ADSCs+H2O2+normal serum), DEX group (ADSCs+H202+DEX drug-containing serum), autophagy agonist group (ADSCs+H2O2+rapamycin (RAP)+normal serum), RAP+DEX group (ADSCs+H2O2+normal serum) , RAP+DEX drug-containing serum), autophagy inhibitor group (ADSCs+H2O2+chloroquine (CQ)+normal serum), CQ+DEX group (ADSCs+H2O2+CQ+DEX drug-containing serum). HO-1, GSH-PX, SOD and CAT in ADSCs under oxidative stress model were measured. ROS fluorescence intensity and apoptosis ratio were detected. Expression of Nrf2, LC3-II/LC3-I and p62 were detected. In vivo, fat mixed with ADSCs or DEX -pretreated ADSCs was implanted subcutaneously in the lower back region of nude mice. Fat grafts were collected and analyzed at 2-, 4-, 6-, and 8-weeks post-transplantation. DEX pretreatment could reduce the expression of p62 to enhance the autophagy level of ADSCs under oxidative stress model. Additionally, cotransplantation of DEX-pretreated ADSCs with fat improved the long-term texture of fat grafts. DEX increased the fat graft survival and angiogenesis.
Keywords: Dexmedetomidine, Adipose-derived stromal cells, anti-oxidative stress, Autophagy, NRF2/P62 pathway, Autologous fat transplantation
Received: 24 Jun 2024; Accepted: 13 Nov 2024.
Copyright: © 2024 Li, Wei, Yang, Ke, Li, Li, Li and Cai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zhongming Cai, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China
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