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Rivastigmine Regulates the HIF-1α/VEGF Signaling Pathway to Induce Angiogenesis and Improves the Survival of Random Flaps in Rats

Random skin flaps are frequently used to repair skin damage. However, the ischemic and hypoxic necrosis limits their wider application. Rivastigmine, a carbamate cholinesterase inhibitor (ChEI), has also been shown to reduce ischemia–reperfusion injury (IRI) and inflammation. This study was performe...

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Autores principales: Liu, Yingying, Li, Wenjie, Ma, Xinyi, He, Jibing, Lin, Yi, Lin, Dingsheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814337/
https://www.ncbi.nlm.nih.gov/pubmed/35126151
http://dx.doi.org/10.3389/fphar.2021.818907
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author Liu, Yingying
Li, Wenjie
Ma, Xinyi
He, Jibing
Lin, Yi
Lin, Dingsheng
author_facet Liu, Yingying
Li, Wenjie
Ma, Xinyi
He, Jibing
Lin, Yi
Lin, Dingsheng
author_sort Liu, Yingying
collection PubMed
description Random skin flaps are frequently used to repair skin damage. However, the ischemic and hypoxic necrosis limits their wider application. Rivastigmine, a carbamate cholinesterase inhibitor (ChEI), has also been shown to reduce ischemia–reperfusion injury (IRI) and inflammation. This study was performed to examine the effect of rivastigmine on flap survival. Sixty male Sprague–Dawley rats with a modified McFarland flap were randomly divided into three groups: control group, 1 ml of solvent (10% DMSO + 90% corn oil); low-dose rivastigmine group (Riv-L), 1.0 mg/kg; and high-dose rivastigmine group (Riv-H), 2.0 mg/kg. All rats were treated once a day. On day 7, the skin flap survival area was measured. After staining with hematoxylin and eosin (H&E), the pathological changes and microvessel density (MVD) were examined. The expression of inflammatory factors IL-1β and IL-18, CD34, hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF) was examined by immunohistochemical staining. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were examined to determine the degree of oxidative stress. Lead oxide/gelatin angiography showed neovascularization and laser Doppler blood flowmetry showed the blood filling volume. Rivastigmine significantly increased the flap survival area and improved neovascularization. CD34, VEGF, and HIF-1α expression were increased, These changes were more pronounced in the Riv-H group. Treatment with rivastigmine reduced the level of MDA, improved SOD activity, and reduced expression of IL-1β and IL-18. Our results indicate that Rivastigmine can increase angiogenesis and significantly improve flap survival.
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spelling pubmed-88143372022-02-05 Rivastigmine Regulates the HIF-1α/VEGF Signaling Pathway to Induce Angiogenesis and Improves the Survival of Random Flaps in Rats Liu, Yingying Li, Wenjie Ma, Xinyi He, Jibing Lin, Yi Lin, Dingsheng Front Pharmacol Pharmacology Random skin flaps are frequently used to repair skin damage. However, the ischemic and hypoxic necrosis limits their wider application. Rivastigmine, a carbamate cholinesterase inhibitor (ChEI), has also been shown to reduce ischemia–reperfusion injury (IRI) and inflammation. This study was performed to examine the effect of rivastigmine on flap survival. Sixty male Sprague–Dawley rats with a modified McFarland flap were randomly divided into three groups: control group, 1 ml of solvent (10% DMSO + 90% corn oil); low-dose rivastigmine group (Riv-L), 1.0 mg/kg; and high-dose rivastigmine group (Riv-H), 2.0 mg/kg. All rats were treated once a day. On day 7, the skin flap survival area was measured. After staining with hematoxylin and eosin (H&E), the pathological changes and microvessel density (MVD) were examined. The expression of inflammatory factors IL-1β and IL-18, CD34, hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor (VEGF) was examined by immunohistochemical staining. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were examined to determine the degree of oxidative stress. Lead oxide/gelatin angiography showed neovascularization and laser Doppler blood flowmetry showed the blood filling volume. Rivastigmine significantly increased the flap survival area and improved neovascularization. CD34, VEGF, and HIF-1α expression were increased, These changes were more pronounced in the Riv-H group. Treatment with rivastigmine reduced the level of MDA, improved SOD activity, and reduced expression of IL-1β and IL-18. Our results indicate that Rivastigmine can increase angiogenesis and significantly improve flap survival. Frontiers Media S.A. 2022-01-21 /pmc/articles/PMC8814337/ /pubmed/35126151 http://dx.doi.org/10.3389/fphar.2021.818907 Text en Copyright © 2022 Liu, Li, Ma, He, Lin and Lin. https://creativecommons.org/licenses/by/4.0/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) and the copyright owner(s) 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.
spellingShingle Pharmacology
Liu, Yingying
Li, Wenjie
Ma, Xinyi
He, Jibing
Lin, Yi
Lin, Dingsheng
Rivastigmine Regulates the HIF-1α/VEGF Signaling Pathway to Induce Angiogenesis and Improves the Survival of Random Flaps in Rats
title Rivastigmine Regulates the HIF-1α/VEGF Signaling Pathway to Induce Angiogenesis and Improves the Survival of Random Flaps in Rats
title_full Rivastigmine Regulates the HIF-1α/VEGF Signaling Pathway to Induce Angiogenesis and Improves the Survival of Random Flaps in Rats
title_fullStr Rivastigmine Regulates the HIF-1α/VEGF Signaling Pathway to Induce Angiogenesis and Improves the Survival of Random Flaps in Rats
title_full_unstemmed Rivastigmine Regulates the HIF-1α/VEGF Signaling Pathway to Induce Angiogenesis and Improves the Survival of Random Flaps in Rats
title_short Rivastigmine Regulates the HIF-1α/VEGF Signaling Pathway to Induce Angiogenesis and Improves the Survival of Random Flaps in Rats
title_sort rivastigmine regulates the hif-1α/vegf signaling pathway to induce angiogenesis and improves the survival of random flaps in rats
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8814337/
https://www.ncbi.nlm.nih.gov/pubmed/35126151
http://dx.doi.org/10.3389/fphar.2021.818907
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