Simvastatin accelerates the healing process of burn wound in Wistar rats through Akt/mTOR signaling pathway
Autor: | Hamidreza Asgari, Sara Simorgh, Maliheh Nobakht, Javad Mohajer Ansari, Azar Babakhani, Mahmood Barati, Mohammad Najafi, Parisa Ramhormozi |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Male Simvastatin Population Pharmacology 03 medical and health sciences Western blot Medicine Animals Rats Wistar education Protein kinase B PI3K/AKT/mTOR pathway education.field_of_study Wound Healing medicine.diagnostic_test business.industry TOR Serine-Threonine Kinases General Medicine Rats 030104 developmental biology Immunohistochemistry 030101 anatomy & morphology Anatomy Wound healing business Myofibroblast Proto-Oncogene Proteins c-akt Developmental Biology medicine.drug Signal Transduction |
Zdroj: | Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft. 236 |
ISSN: | 1618-0402 |
Popis: | 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-AktThr308, P-mTORSer2448, and P-p70S6 KThr389 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. |
Databáze: | OpenAIRE |
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