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    標題: Exendin-4在糖尿病大鼠模型中對傷口癒合之影響
    Effects of exendin-4 on wound healing in diabetes rat model
    作者: 鄭涵妮
    貢獻者: 生物科技系
    郭玫君
    阮俊能
    關鍵字: Exendin-4
    昇糖素
    糖尿病
    傷口癒合
    Exendin-4
    GLP-1
    diabetes
    wound healing
    日期: 2016
    上傳時間: 2016-12-21 15:28:36 (UTC+8)
    摘要: 本論文目的為研究一種GLP-1R類似物exendin-4 (Ex4),對於糖尿病模型大鼠切除性傷口之促進癒合潛力。傷口手術前72小時,以腹腔注射鏈佐酶素 (Streptozotocin,STZ),誘導大鼠糖尿病模型,之後在其背部開創傷口,2*2 cm2,隨機分組給予安慰劑或是GLP-1R類似物exendin-4 (以腹腔注射低濃度劑量0.5 g/公斤/天)連續治療兩週。術後癒合程度會與原始傷口面積以比例換算進行比較;測量術後第三天與第十四天傷口組織中的超氧陰離子 (Superoxide anions)與前發炎 (Pro-inflammatory)細胞激素,以了解不同傷口癒合進程的發炎狀況,並測定前血管新生因子與細胞外基質以評估血管新生 (Angiogenesis)表現。結果發現經低濃度劑量治療,可在不影響血糖下,顯著抑制糖尿病傷口組織發炎;同時在術後第十一天以18G針頭將matrigel植入大鼠腹部皮下,在術後第十四天犧牲分析,從定性外觀與matrigel血紅素分析也證實exendin-4能幫助微血管新生;exendin-4連續治療14天後,能讓糖尿病鼠傷口組織中的促血管內皮生長因子受體-2 (Vascular endothelial growth factor receptor 2,VEGFR2)、磷酸化内皮型一氧化氮合酶 (Endothelial nitric oxide synthase,eNOS)、基質金屬蛋白酶 (Matrix metalloproteinase-2,MMP-2)與轉型生長因子 (Transforming growth factor,TGF-)蛋白質表現量上升;傷口組織切片結果也證明exendin-4促進血管形成,並能夠影響皮膚表皮層與真皮層細胞增殖。結論利用GLP-1R類似物exendin-4治療後,經由減緩早期發炎、促進增殖期血管新生並增強成熟期TGF-/MMP路徑表現,最後改善糖尿病傷口癒合。
    This study investigated the therapeutic potential of exendin-4, a GLP-1 receptor analogue, in a diabetic rat model of excisional wound injury. After creation of wound on the dorsal skin, the streptozotocin-induced diabetic rats were randomly assigned to receive saline or a GLP-1R analogue (exendin-4, 0.5 g/kg/d, i.p.) for 2 weeks. Wound healing was compared by measuring the final-to-initial wound area ratio. Generation of superoxide anions and pro-inflammatory cytokines in the wound was determined. Levels of angiogenesis, expressions of pro-angiogenic factors and extracellular matrix were assayed. Treatment with exendin-4 restored the wound closure in diabetic rats, and significantly suppressed the tissue generation of superoxide anions and interleukins (IL)-6 in the wounds. Circulating endothelial progenitor (CD34+/KDR+) cells increased significantly and the in vivo matrigel assay also demonstrated increased capillary tube formation. Expressions of VEGFR2, phosphorylated eNOS, MMP-2 and TGF- were enhanced during .the wound healing phases. Histological examination confirmed that enxedin-4 enhanced vascularity, dermal and epidermal regeneration, and increased proliferative cells in the dermis. Agonism of GLP-1R using exendin-4 attenuates inflammatory response and enhances angiogenesis at the early proliferation phases, and augments the TGF-/MMP regenerative pathway at the maturation phase of diabetic wound healing.
    關聯: 網際網路公開:2021-06-14,學年度:104,65頁
    Appears in Collections:[生物科技系(所)] 博碩士論文

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