Simvastatin accelerates the healing process of burn wound in Wistar rats through Akt/mTOR signaling pathway.

Autor: Ramhormozi P; Student Research Committee, Iran University of Medical Sciences, Shahid Hemmat Highway, Tehran, 1449614535, Iran; Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Shahid Hemmat Highway, Tehran, 1449614535, Iran. Electronic address: Parisa.ramhormozi@yahoo.com., Ansari JM; Department of Anatomy, School of Medicine, Hormozgan, University of Medical Sciences, Jomhuri Eslami Blvd, Bandar Abbas, 7919915519, Iran. Electronic address: javadmansari@gmail.com., Simorgh S; Department of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Shahid Hemmat Highway, Tehran, 1449614535, Iran. Electronic address: srsimorgh@gmail.com., Asgari HR; Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Shahid Hemmat Highway, Tehran, 1449614535, Iran., Najafi M; Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, Shahid Hemmat Highway, Tehran, 1449614535, Iran., Barati M; Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Shahid Hemmat Highway, Tehran, 1449614535, Iran. Electronic address: mahmood.barati@gmail.com., Babakhani A; Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Shahid Hemmat Highway, Tehran, 1449614535, Iran. Electronic address: azarbabakhany@yahoo.com., Nobakht M; Department of Anatomical Sciences, School of Medicine, Iran University of Medical Sciences, Shahid Hemmat Highway, Tehran, 1449614535, Iran; Antimicrobial Resistance Research Center, Immunology & Infectious Disease Research Institute, Iran University of Medical Sciences, Shahid Hemmat Highway, Tehran, 1449614535, Iran. Electronic address: nobakht.m@iums.ac.ir.
Jazyk: angličtina
Zdroj: Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft [Ann Anat] 2021 Jul; Vol. 236, pp. 151652. Date of Electronic Publication: 2020 Dec 02.
DOI: 10.1016/j.aanat.2020.151652
Abstrakt: Statins, apart from cholesterol-lowering properties, have wound healing effects. Hereby, we aimed to assess the impact of Simvastatin (SMV), one of the most commonly used statins, on Akt/mTOR signaling pathway during burn wound healing process. After creating a second-degree burn on the dorsal area of adult male Wistar rats (n = 60), they were randomly divided into the control, SMV, vehicle of Simvastatin (SMV-Veh), Rapamycin (RM), vehicle of Rapamycin (RM-Veh), and combined SMV and RM (SMV + RM) groups. The animals were sacrificed on the 7th and 14th post-burn days and wound tissue samples were collected for histologic, immunohistochemical, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot investigations. Rapamycin (RM) was also used to treat animals as an mTOR inhibitor. Topical administration of SMV resulted in a faster healing rate, elevated collagen deposition, and increased myofibroblast population compared to other experimental groups. Moreover, qRT-PCR findings showed that the wounds treated with SMV alone had the highest expression levels of CD31, VEGF, Akt, mTOR, and p70S6K after 7 and 14 days of burn model (p < 0.001). According to western blot findings, daily topical treatment with SMV further increased protein levels of P-Akt Thr308 , P-mTOR Ser2448 , and P-p70S6 K Thr389 compared with other treatments, at both follow-up time points (p < 0.001). In contrast, inhibition of Akt/mTOR signaling pathway by RM reduced SMV-induced wound healing process. Seemingly, SMV promotes burn wound healing, at least in part, through activating Akt/mTOR signaling pathway, suggesting topically applied SMV as an alternative therapeutic approach for managing burn wound healing.
(Copyright © 2020. Published by Elsevier GmbH.)
Databáze: MEDLINE
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