The mechanism of Qufushengxin ointment in promoting chronic wound healing by regulating autophagy and angiogenesis, and improving wound microenvironment through the PI3K/Akt/mTOR pathway
摘要
Certain cellular and molecular mechanisms must be triggered to aid in closing chronic wounds. In this study, we investigated the role of most important mechanisms, including the PI3K/Akt/mTOR signaling, autophagy, and angiogenesis in chronic wound healing following the use of MEBO cream and Qufushengxin Ointment as a traditional Chinese medicinal formulation for wound healing. 100 male SPF SD rats (12 weeks old) were sourced and chronic wound models were created through a full-thickness skin defect method and hormone injection, followed by anesthesia and wound treatment. The rats were divided into four groups: a control group receiving saline and three treatment groups receiving different ointments. Wounds were monitored and treated daily, with tissue samples collected at 3, 7, and 14 days for histological analysis and immunohistochemical evaluations. RNA was extracted from excised tissues for real-time PCR to assess gene expression changes. The healing rate was calculated based on wound area measurements, and various histopathological techniques were employed to analyze tissue morphology and protein expression, ensuring comprehensive evaluation of the wound healing process, depending on the activation of the corresponding mechanisms. The rats received ointment healed faster than the control group, which Qufu Shengxin Ointment consistently outperformed topical recombinant human basic fibroblast growth factor (TRHBFGF) under the brand name of TRHBFGF. Specifically, intervention groups had higher levels of PI3K/Akt/mTOR, especially MEBO and Qufu Shengxin Ointment. Moreover, these groups demonstrated overexpressed autophagy-related indices ULK1, Beclin1, and LC3-II. They also had higher HIF-1α and VEGF, while lower TNF-α. MEBO and Qufu Shengxin Ointment consistently outperformed TRHBFGF across multiple markers. Enhanced PI3K/Akt/mTOR signaling, autophagy, and HIF-1α/VEGF expression, particularly in MEBO and Qufu Shengxin Ointment groups, were associated with improved wound healing.