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"Single intraosseous injection of simvastatin promotes endothelial progenitor cell mobilization, neovascularization, and wound healing in diabetic rats".

BACKGROUND
This study explored the effect of a single local intraosseous application of a small dose simvastatin on the wound healing process in type 1 diabetic rats and related mechanisms.


METHODS
We chose the streptozotocin-induced type 1 diabetic rat to establish a full thickness dermal wound using a 12-mm diameter sterile disposable punch. The rats (n=32) were randomly divided into four groups: (1) Normal control rats, (2) type 1 diabetic rats with an intraosseous injection of hydrogel vehicle or (3) simvastatin (0.5 mg), and (4) with intragastric administration of simvastatin (20 mg/kg·d). Wound closure was followed by digital planimetry. Mobilization of endothelial progenitor cells into circulatory system was studied using fluorescence activated cell sorter (FACS). Neovasculization was analyzed with immunofluorescence histochemical staining. The relative levels of adiponectin and stromal cell-derived factor 1 (SDF-1) in serum, bone and wound tissues were examined via ELISA and western blot.


RESULTS
Diabetic rats exhibited impaired wound healing. Intraosseous administration of simvastatin accelerated wound healing beginning at day 4 and angiogenesis was more obvious than in the control group. ELISA revealed that adiponectin concentrations in T1DM+SIM 0.5 mg group were significantly higher compared with the T1DM group beginning at day 4. Intraosseous administration of simvastatin decreased the expression of adiponectin (APN) and SDF-1 in bone tissue but enhanced the expression of APN in wounded skin.


CONCLUSIONS
A single local intraosseous application of simvastatin promotes wound healing in type 1 diabetic rat. The underlying mechanisms may be attributed to the regulation of the APN/SDF-1 pathway, which plays a pivotal role in endothelial progenitor cell mobilization and angiogenesis.