探討小孢子靈芝免疫調節蛋白GMI在STZ誘導糖尿病小鼠之傷口癒合治療效果

糖尿病是全球性的健康問題，而在台灣也是如此。糖尿病患者人數和流行率不斷增加。糖尿病併發症包括神經病變、大小血管病，以及傷口癒合緩慢都是常見的問題。本研究的目的是研究重組GMI（rGMI）蛋白對糖尿病傷口癒合的治療效果。GMI是小孢子靈芝（Ganoderma microsporum）所分離出來的真菌免疫調節蛋白。本研究為評估rGMI對於傷口癒合的效果，在細胞實驗中，使用三種細胞HaCaT (角質細胞) 、NIH / 3T3 (纖維母細胞) 和RAW264.7(巨噬細胞) 做細胞癒合實驗和細胞增生率實驗，以及在動物實驗使用小鼠傷口癒合動物模式。結果顯示低濃度rGMI (< 0.075M) 對於HaCaT和NIH / 3T3細胞的癒合效果均有促進趨勢，但在RAW264.7則無。rGMI也會促進HaCaT和RAW264.7細胞增生。然而在動物實驗中，我們以背部穿刺小鼠皮膚製造兩個對稱性的圓形傷口，結果顯示rGMI (0.05mg/mL) 加速了的正常C57BL6小鼠和STZ誘導之糖尿病小鼠的傷口癒合過程。在正常小鼠中，rGMI組與對照組相比，傷口在第3天和第4天有顯著較小約15％和12％。而在糖尿病小鼠中則是在第4天傷口有顯著較小約17％。綜合結果顯示了rGMI可幫助加速癒合過程。

關鍵字

糖尿病；傷口癒合；小孢子靈芝免疫調節蛋白

並列摘要

Diabetes mellitus (DM) is a worldwide health issue, in Taiwan as well. DM patient numbers and prevalence are keeping increasing. Diabetic complications, including neuropathy, large and small vascular disease, slow healing of wound are very common symptoms. The purpose of this study is to investigate the therapeutic effects of recombinant Ganoderma microsporum immunomodulatory (rGMI) protein on DM-induced wound healing and hopefully it can be a therapeutic candidate to treat DM patients in the future. GMI is derived from fungus Ganoderma microsporum. To characterize the healing effect, we evaluated the in vitro healing effects of rGMI on three types of cells including HaCaT (keratinocytes), NIH/3T3 (fibroblasts) and RAW264.7 (macrophages) as well the wound healing assessments in animal model. Our results indicated that low concentration (< 0.075M) of rGMI increased healing process for both cell lines HaCaT and NIH / 3T3 , but not RAW264.7 cells. Furthermore, rGMI also promoted HaCaT and RAW264.7 cell growth and proliferation. Moreover, rGMI also accelerated the healing process on punch-induced wounds on the dorsal part of STZ–induced (streptozotocin) diabetic mice. This rGMI-induced healing efficacy were also observed in normal mice. In healing assessment on normal mice, our data indicated that the lesions shrank faster with 15% and 12% reduction in wound area with administration of rGMI compared to the placebo at day 3 and 4. However, the enhanced wound healing process was observed at day 4 and the wounded area displayed with 17% reduction in lesions compared to control lesions. Taken together, our preliminary data suggest that rGMI may accelerate healing process of skin wounds mechanically induced by punch on animals.

並列關鍵字

Diabetes mellitus ； Wound healing ； Recombinant Ganoderma microsporum Immunomodulatory Protein (rGMI)

參考文獻

國民健康署. (2013-2016). 國民營養健康狀況變遷調查.

Aldo A. Rossini, J. P. M., and Arthur A. Like. (1985). Immunology of Insulin-Dependent Diabetes Mellitus. Annu Rev Immunol, 3, 289-320.

Bagdade, J. D., Root, R. K., & Bulger, R. J. (1974). Impaired Leukocyte Function in Patients with Poorly Controlled Diabetes. Diabetes, 23(1), 9-15.

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Fowler, M. J. (2008). Microvascular and Macrovascular Complications of Diabetes. Clinical Diabetes, 26(2), 77-82.

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探討小孢子靈芝免疫調節蛋白GMI在STZ誘導糖尿病小鼠之傷口癒合治療效果

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