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.

他汀类药物除了具有降低胆固醇的特性外，还具有伤口愈合作用。因此，我们旨在评估最常用的他汀类药物之一辛伐他汀 (SMV) 在烧伤伤口愈合过程中对 Akt/mTOR 信号通路的影响。在成年雄性 Wistar 大鼠（n = 60）的背部产生二度烧伤后，将它们随机分为对照、SMV、辛伐他汀载体（SMV-Veh）、雷帕霉素（RM）、雷帕霉素载体（ RM-Veh)，以及合并的 SMV 和 RM (SMV + RM) 组。在烧伤后第 7 天和第 14 天处死动物，收集伤口组织样本用于组织学、免疫组织化学、定量实时聚合酶链反应 (qRT-PCR) 和蛋白质印迹研究。雷帕霉素 (RM) 也用于治疗动物作为 mTOR 抑制剂。与其他实验组相比，SMV 的局部给药导致更快的愈合速度、增加的胶原沉积和增加的肌成纤维细胞数量。此外，qRT-PCR 结果显示，仅用 SMV 治疗的伤口在烧伤模型 7 天和 14 天后 CD31、VEGF、Akt、mTOR 和 p70S6K 的表达水平最高。p < 0.001)。根据蛋白质印迹结果，在两个随访时间点，与其他治疗相比，每天用 SMV 局部治疗进一步增加了 P-Akt ^Thr308、P-mTOR ^Ser2448和 P-p70S6 K ^{Thr389 的}蛋白质水平（p < 0.001）。相反，RM 对 Akt/mTOR 信号通路的抑制减少了 SMV 诱导的伤口愈合过程。表面上，SMV 至少部分通过激活 Akt/mTOR 信号通路促进烧伤伤口愈合，表明局部应用 SMV 作为管理烧伤伤口愈合的替代治疗方法。