| 段 鹏,许 静,刘 利,屈 慧,马 丽,杜俊凯.ADSCs联合Exendin-4治疗糖尿病大鼠创面愈合的机制研究[J].,2020,(20):3807-3814 |
| ADSCs联合Exendin-4治疗糖尿病大鼠创面愈合的机制研究 |
| Study on the Mechanism of ADSCs Combined with Exendin-4 in the Treatment of Wound Healing in Diabetic Rats |
| 投稿时间：2020-04-22 修订日期：2020-05-17 |
| DOI：10.13241/j.cnki.pmb.2020.20.002 |
| 中文关键词: 糖尿病 创面愈合 脂肪组织衍生的干细胞 Exendin-4 血管生成 内皮细胞 |
| 英文关键词: Diabetes Wound healing Adipose-derived stem cells Exendin-4 Angiogenesis Endothelial cells |
| 基金项目:陕西省自然科学基础研究计划项目（2018JM7152；2018JM7021）；西安交通大学第一附属医院基金自由探索项目（2019ZYTS-10） |
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| 中文摘要: |
| 摘要 目的：探究ADSCs联合Exendin-4治疗糖尿病大鼠创面愈合的效果及可能机制。方法：通过高脂饲料喂养和腹腔注射链脲佐菌素（STZ，45 mg/kg）建立糖尿病SD大鼠模型。使用直径1 cm的皮肤打孔活检器在大鼠背部制作创面。将72只建模成功的大鼠随机分为糖尿病组、ADSCs组、Exendin-4组和ADSCs+Exendin-4组，每组18只。未建模的20只大鼠作为对照组。皮肤创伤后1天，按照指定给药方案进行给药，每天给药1次，共14天。检测治疗后大鼠的血糖、创面愈合率、微血管密度、创面组织学改变和血管生成因子（VEGF-A、VEGFR-2、PDGF-BB、PDGFR-β和HIF-1α）的蛋白表达水平。另外，将HUVEC细胞分为对照组、高糖组、ADSCs组、Exendin-4组和ADSCs+Exendin-4组，并对各组细胞进行相应的处理。检测了ADSCs和Exendin-4对缺氧和高糖培养的HUVEC的增殖、迁移和血管生成的影响。结果：ADSCs和/或Exendin-4治疗组大鼠的血糖水平与糖尿病组无显著差异（P>0.05）。与单独治疗组相比，ADSCs+Exendin-4组的创面愈合率、微血管密度和创面组织中VEGF-A、VEGFR-2、PDGF-BB、PDGFR-β和HIF-1α的蛋白表达水平显著升高（P<0.05）。与单独治疗组的HUVEC相比，ADSCs+Exendin-4组的HUVEC的增殖、迁移和血管生成能力显著提高，并且血管生成因子的表达水平明显上调（P<0.05）。结论：对糖尿病大鼠创面组织局部施用ADSCs和Exendin-4可明显促进创面愈合。ADSCs和Exendin-4通过促进内皮细胞的增殖、迁移及血管生成因子的分泌来促进血管生成和创面愈合。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect and possible mechanism of ADSCs combined with Exendin-4 in the treatment of wound healing in diabetic rats. Methods: The diabetic SD rat model was established by feeding high-fat feed and intraperitoneal injection of streptozotocin (STZ, 45 mg / kg). A skin punch biopsy with a diameter of 1 cm was used to make a wound on the back of the rat. 72 successfully modeled rats were randomly divided into diabetes group, ADSCs group, Exendin-4 group and ADSCs + Exendin-4 group, 18 rats in each group. 20 unmodeled rats served as a control group. One day after skin trauma, the drug was administered according to the prescribed dosing regimen, once a day for 14 days. After treatment, the blood glucose, wound healing rate, microvessel density, wound histology changes and protein expression of angiogenic factors (VEGF-A, VEGFR-2, PDGF-BB, PDGFR-β and HIF-1α) were detected. In addition, HUVEC cells were divided into control group, high glucose group, ADSCs group, Exendin-4 group and ADSCs + Exendin-4 group, and the cells were treated accordingly. The effects of ADSCs and Exendin-4 on the proliferation, migration and angiogenesis of HUVEC cultured in hypoxia and high glucose were examined. Results: There was no significant difference in blood glucose levels between ADSCs and/or Exendin-4 treatment group and diabetes group (P>0.05). Compared with the single treatment group, the wound healing rate, microvessel density and protein expression levels of VEGF-A, VEGFR-2, PDGF-BB, PDGFR-β and HIF-1α in the ADSCs + Exendin-4 group were significantly increased (P<0.05). Compared with HUVEC in the single treatment group, the proliferation, migration, and angiogenic capacity of HUVEC in the ADSCs + Exendin-4 group were significantly improved, and the expression level of angiogenic factors was significantly increased (P<0.05). Conclusion: Local application of ADSCs and Exendin-4 in the wound tissues of diabetic rats can obviously promote wound healing. ADSCs and Exendin-4 promote angiogenesis and wound healing by promoting the proliferation and migration of endothelial cells and the secretion of angiogenic factors. |
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