Effects of Moist Exposed Burn Ointment on Wound Neovascularization and Plasma Exosomal mir-31-5p in Diabetic Mice

Moist-exposed burn ointment (MEBO) is a traditional Chinese medicine used to treat chronic diabetic wounds; however, the underlying mechanism is unclear. Recent evidence suggests the role of exosomes and functional miRNAs in wound neovascularization. Here, we aimed to investigate the effects of MEBO on wound neovascularization and plasma exosomal mir-31-5p (pExo-mir-31-5p) expression in diabetic mice. A total of 120 C57BL/6 mice were randomly divided into a non-diabetic control group (n = 24) and a diabetic group induced by streptozotocin (n = 96), which was further randomized into diabetic control, MEBO, beifuxin, and MHY1485 groups (n = 24 each). Five groups were established with full-thickness skin resection models, which were treated with physiologic saline, physiologic saline, MEBO, beifuxin, and MHY1485, respectively. On days 1, 7, 13, and 18, the wound closure rate, microvessel density, and pExo-mir-31-5p expression levels, together with VPS4a and Rab27a mRNA and protein levels in wound tissues, were analyzed using ImageJ, hematoxylin-eosin (HE) staining, quantitative real-time polymerase chain reaction (qPCR) and western blot (WB), respectively. Furthermore, correlations between the expression of VPS4a, Rab27a protein, pExo-mir-31-5p, and microvessel density were analyzed. We found that MEBO promoted wound repair in diabetic mice (p < 0.050). It enhanced wound neovascularization during the early and middle stages of wound healing but inhibited it during the later stage (p < 0.050). MEBO upregulated Vps4a and Rab27a mRNA and protein expression in wound tissues, as well as pExo-mir-31-5p during the early and intermediate stages of healing, while downregulating them in the later stage (p < 0.050). Moreover, VPS4a, Rab27a protein, pExo-mir-31-5p expression, and microvessel density were positively correlated in MEBO-treated mice (p < 0.050). In conclusion, MEBO dynamically regulates wound neovascularization and pExo-mir-31-5p expression in diabetic mice, providing new theoretical support for its clinical application.