Maggot extract accelerates skin wound healing of diabetic rats via enhancing STAT3 signaling

Abstract

Background Diabetic skin wound is a complex problem due to the disruption of normal repairing program and lack of effective remedy. Lucilia sericata larvae (maggot) is a folk method to treat chronic skin wound, while its therapeutic effects on that caused by diabetic remains unknown. Objective This study aims to investigate the therapeutic effects of maggot extract (M.E.) on diabetic skin wound and its molecular mechanism by establishing the skin wound model of diabetic Sprague Dawley (SD) rats. Methods Diabetic model was established by injecting intraperitoneally streptozotocin in SD rats under specific pathogen-free (SPF) conditions. The rat fasting blood glucose values were ≧16.7 mmol/L 72 hours after intraperitoneal streptozotocin (60mg/kg body weight) injection. The rats were divided into five groups (n = 10/group): normal group: normal SD rats without any treatment, diabetic blank group: the diabetic rats without any treatment, Vaseline group: the diabetic rats dressed with Vaseline, recombinant human epidermal-growth-factor (rhEGF) group: the diabetic rats dressed with a mixture of Vaseline and 200 μg/g rhEGF, M.E. group: the diabetic rats dressed with a mixture of Vaseline and 150 μg/ml maggot extract. The round open wounds (1.0 cm in diameter) down to the muscle fascia were made on both sides of rat dorsa by removing the skin layer (epidermis and dermis) and were daily photographed for calculating their healing rates. Hematoxylin-eosin (HE) and Masson’s trichrome staining were performed on skin wound sections to analyze re-epithelialization and granulation tissue formation. Immunohistochemical (IHC), immunofluorescent (IF) stainings and Western blotting were conducted to analyze the statuses of STAT3 signaling. Results The average wound healing rates on the 14th day were 91.7% in the normal, 79.6% in M.E., 71% in rhEGF, 55.1% in vaseline and 43.3% in the diabetes blank group. Morphological staining showed more active granulation tissue formation, re-epithelialization and neovascularization in M.E.-group than those in the blank and the vaseline-treated groups. Decreased p-STAT3 nuclear tranlocation and down-regulated Bcl-2, CyclinD1 and vascular endothelial growth factor (VEGF) expression were evidenced in the diabetic rats, which could be improved by rhEGF and especially M.E. Conclusion Maggot extract would be an alternative and/or adjuvant candidate for the better management of diabetic skin wounds because of its activity in enhancing STAT3 activation.