[논문]Metformin accelerates wound healing in type 2 diabetic db/db mice

Han, Xue; Tao, Yulong; Deng, Yaping; Yu, Jiawen; Sun, Yuannan; Jiang, Guojun

doi:10.3892/mmr.2017.7707

Metformin accelerates wound healing in type 2 diabetic db/db mice 원문보기

Molecular medicine reports, v.16 no.6, 2017년, pp.8691 - 8698

Han, Xue (Department of Pharmacy, Xiaoshan Hospital, Hangzhou, Zhejiang 311202, P.R. China) , Tao, Yulong (Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China) , Deng, Yaping (Department of Pharmacy, Xiaoshan Hospital, Hangzhou, Zhejiang 311202, P.R. China) , Yu, Jiawen (Department of Pharmacy, Xiaoshan Hospital, Hangzhou, Zhejiang 311202, P.R. China) , Sun, Yuannan (Department of Pharmacy, Xiaoshan Hospital, Hangzhou, Zhejiang 311202, P.R. China) , Jiang, Guojun (Department of Pharmacy, Xiaoshan Hospital, Hangzhou, Zhejiang 311202, P.R. China)

Abstract ▼ AI-Helper

Wound healing impairment is increasingly recognized to be a consequence of hyperglycemia-induced dysfunction of endothelial precursor cells (EPCs) in type 2 diabetes mellitus (T2DM). Metformin exhibits potential for the improvement of endothelial function and the wound healing process. However, the underlying mechanisms for the observed beneficial effects of metformin application remain to be completely understood. The present study assessed whether metformin, a widely used therapeutic drug for T2DM, may accelerate wound closure in T2DM db/db mice. Genetically hyperglycemic db/db mice were used as the T2DM model. Metformin (250 mg/kg/day; intragastric) was administered for two weeks prior to EPC collection and wound model creation in db/db mice. Wound healing was evaluated by alterations in the wound area and the number of platelet endothelial cell adhesion molecule-positive cells. The function of the isolated bone marrow-derived EPCs (BM-EPCs) was assessed by a tube formation assay. The number of circulating EPCs, and the levels of intracellular nitric oxide (NO) and superoxide (O2−) were detected by flow cytometry. Thrombospondin-1 (TSP-1) expression was determined by western blot analysis. It was observed that treatment with metformin accelerated wound healing, improved angiogenesis and increased the circulating EPC number in db/db mice. In vitro, treatment with metformin reversed the impaired BM-EPC function reflected by tube formation, and significantly increased NO production while decreasing O2− levels in BM-EPCs from db/db mice. In addition, TSP-1 expression was markedly attenuated by treatment with metformin in cultured BM-EPCs. Metformin contributed to wound healing and improved angiogenesis in T2DM mice, which was, in part, associated with stimulation of NO, and inhibition of O2− and TSP-1 in EPCs from db/db mice.

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참고문헌 (50)

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Metformin accelerates wound healing in type 2 diabetic db/db mice 원문보기

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