基于Wnt/β-catenin信号通路的三七/白及胶海绵促进糖尿病足溃疡模型大鼠创面愈合的作用机制研究
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篇名: 基于Wnt/β-catenin信号通路的三七/白及胶海绵促进糖尿病足溃疡模型大鼠创面愈合的作用机制研究
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摘要: 目的:研究三七/白及胶海绵促进糖尿病足溃疡(DFU)模型大鼠创面愈合的作用机制。方法:取健康SD大鼠,采用高脂高糖饲料喂养、一次性腹腔注射链脲佐菌素建立糖尿病模型,再以钕铁硼磁铁压轧大鼠背部制作溃疡创面造成DFU模型。将60只DFU模型大鼠随机分为A组(空白组,即生理盐水纱布组)、B组(凡士林纱布组)、C组(明胶海绵组)、D组(三七/白及胶海绵组),每组15只。各组大鼠分别给予相应纱布/敷料覆盖创面进行干预治疗,每1~2天换药1次。干预治疗后第3、7天时,分别肉眼观察各组大鼠创面愈合情况并计算创面愈合率;采集创缘组织制作苏木精-伊红(HE)染色切片,在显微镜下进行组织病理学观察;采用实时荧光定量聚合酶链式反应(RT-PCR)法测定创面组织中β-连环素(β-catenin)、糖原合成激酶-3β(GSK-3β)、R-脊椎蛋白3(Rspo3)的mRNA表达水平。结果:干预治疗后第3、7天时,与A、B、C组分别比较,D组大鼠创面愈合率显著升高(P<0.05);创面组织的炎细胞浸润、胶原纤维沉积、毛细血管和肉芽组织生长均明显增加;β-catenin、Rspo3的mRNA表达水平均有升高,GSK-3β的mRNA表达水平均有降低,且除了干预治疗后第3天时的β-catenin和第7天时的GSK-3β与C组比较差异不显著外,其余指标差异均有统计学意义(P<0.05)。结论:三七/白及胶海绵可有效促进DFU模型大鼠溃疡创面愈合;其作用机制可能与Wnt/β-catenin 通路中β-catenin、Rspo3的mRNA表达的上调和GSK-3β的mRNA表达的下调相关。
ABSTRACT: OBJECTIVE: To study the mechanism of wound healing promotion of Panax notoginseng-Bletilla striata gum sponge on diabetic foot ulcer (DFU) model rats. METHODS: Healthy SD rats were selected and given high-lipid and high-glucose diet, intraperitoneal injection of streptozotocin once to establish diabetes model. Neodymium-iron-boron magnet was used to press the back of rats to make ulcer wound then established DFU model. Totally 60 DFU model rats were randomly divided into group A(blank group, i.e. normal saline gauze group), group B(vaseline gauze group),group C (gelatin sponge group) and group D (P. notoginseng-B. striata gum sponge group), with 15 rats in each group. The rats were given corresponding gauze/sponge to cover the wound for intervention treatment, changing dressing once every 1-2 days. On the 3rd and 7th day after intervention, the wound healing of rats in each group was observed with naked eyes, and the wound healing rate was calculated. The wound margin tissue was collected to obtain HE staining section, and histopathological observation was conducted under microscope. mRNA expression of β-catenin, GSK-3β and Rspo3 in wound tissue were determined by RT-PCR. RESULTS: On the 3rd and 7th day after intervention, compared with group A, B, C, healing rate of group D was increased significantly (P<0.05); inflammatory cell infiltration, collagen deposition, capillary and granulation tissue growth in wound tissue increased significantly. The mRNA expression levels of β-catenin and Rspo3 all increased, and those of GSK-3β all decreased; except for the difference of β-catenin at the 3rd day and GSK-3β at the 7th day after intervention between group D and group C were not significant, the difference of other indicators was statistically significant (P<0.05). CONCLUSIONS: P. notoginseng-B. striata gum sponge can effectively promote the wound healing in DFU model rats, the mechanism of which may be associated with up-regulating the expression of β-catenin and Rspo3 mRNA and down-regulating the expression of GSK-3β mRNA.
期刊: 2019年第30卷第4期
作者: 雷霆,孙东旭,周军,魏海梁,张习禄,陈志国
AUTHORS: LEI Ting,SUN Dongxu,ZHOU Jun,WEI Hailiang,ZHANG Xilu,CHEN Zhiguo
关键字: 三七/白及胶海绵;糖尿病足溃疡;创面;促愈合;Wnt/β-catenin通路;机制;大鼠
KEYWORDS: Panax notoginseng-Bletilla striata gum sponge; Diabetic foot ulcer; Wound; Healing promotion; Wnt/β-catenin pathway; Mechanism; Rat
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