紫檀芪对糖尿病性皮肤溃疡模型大鼠创面愈合的影响及机制
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篇名: 紫檀芪对糖尿病性皮肤溃疡模型大鼠创面愈合的影响及机制
TITLE: Effects and mechanism of pterostilbene on wound healing in diabetic skin ulcer model rats
摘要: 目的 探究紫檀芪(PTE)对糖尿病性皮肤溃疡模型大鼠创面愈合的影响及机制。方法取10只SD大鼠为对照组,其余大鼠以饲喂高脂高糖饲料+腹腔注射链脲佐菌素+剪去背部标记区域皮肤及皮下组织建立糖尿病性皮肤溃疡模型后,随机分为模型组、PTE低剂量组(40mg/kg)、PTE高剂量组(80mg/kg)和PTE高剂量+PP2组(80mg/kg的PTE+2mg/kg的SRC抑制剂PP2),每组10只。于建模后第2天,各药物组大鼠腹腔注射相应药液,对照组和模型组大鼠腹腔注射生理盐水,每天1次,连续14d。测算各组大鼠给药第7、14天的创面愈合率,检测血清中白细胞介素1β(IL-1β)、IL-6、肿瘤坏死因子α(TNF-α)、血管内皮生长因子(VEGF)含量,观察创面肉芽组织的病理变化并检测创面肉芽组织中SRC/促分裂原活化的蛋白激酶激酶(MEK)/胞外信号调节激酶(ERK)信号通路相关蛋白的表达。结果与对照组比较,模型组大鼠的创面愈合率、血清中VEGF含量和创面肉芽组织中SRC、MEK1/2、ERK1/2的磷酸化水平均显著降低(P<0.05),血清中IL-1β、IL-6、TNF-α含量均显著升高(P<0.05),创面肉芽组织中有明显的炎症细胞浸润,新生血管减少;与模型组比较,PTE低、高剂量组大鼠上述指标均显著改善(P<0.05),创面肉芽组织的病理损伤均明显改善;PP2显著逆转了高剂量PTE对上述指标的改善作用(P<0.05)。结论PTE能促进糖尿病性皮肤溃疡模型大鼠的创面愈合,其作用机制可能与激活SRC/MEK/ERK信号通路有关。
ABSTRACT: OBJECTIVE To explore the effects of pterostilbene (PTE) on wound healing in diabetic skin ulcer model rats and its mechanism. METHODS Ten SD rats were grouped into control group; after diabetic skin ulcer model of other rats was induced by giving high-fat and high-sugar diet+intraperitoneal injection of streptozotocin+cutting off the skin and subcutaneous tissue in the marked area of the back, model rats were randomly divided into model group, PTE low-dose group (40 mg/kg), PTE high-dose group (80 mg/kg), PTE high-dose+PP2 group (80 mg/kg PTE+2 mg/kg SRC inhibitor PP2), with 10 rats in each group. On the second day after modeling, the rats in each drug group were intraperitoneally injected with corresponding drug solutions, while the rats in control group and model group were intraperitoneally injected with normal saline, once a day, for 14 consecutive days. The wound healing rate of rats in each group was measured on the 7th and 14th day of administration; the contents of interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) in the serum of rats were detected; the pathological changes of wound granulation tissue were observed, and the expressions of SRC/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway-related proteins in wound granulation tissue were detected. RESULTS Compared with control group, the wound healing rate, serum content of VEGF, the phosphorylation levels of SRC, MEK1/2 and ERK1/2 were decreased significantly (P<0.05), while serum contents of IL- 1β, IL-6 and TNF-α were increased significantly (P<0.05); there was obvious infiltration of inflammatory cells in the wound granulation tissue, and the number of new blood vessels decreased. Compared with model group, above indexes of PTE low-dose and high-dose groups were improved significantly (P<0.05), and the pathological injury of granulation tissue in wound was improved. PP2 significantly reversed the improvement effects of PTE on the above indexes (P<0.05). CONCLUSIONS PTE can promote the wound healing of diabetic skin ulcer model rats, the mechanism of which may be related to activating SRC/MEK/ERK signaling pathway.
期刊: 2023年第34卷第16期
作者: 刘亚坤;李刚;颜娟;徐会志;吴彦江;尤帅;牛静亚;李洪健;张丙贵
AUTHORS: LIU Yakun, LI Gang,YAN Juan,XU Huizhi,WU Yanjiang,YOU Shuai,NIU Jingya,LI Hongjian,ZHANG Binggui
关键字: 紫檀芪;糖尿病性皮肤溃疡;创面愈合;SRC/促分裂原活化的蛋白激酶激酶/胞外信号调节激酶信号通路
KEYWORDS: pterostilbene; diabetic skin ulcer; wound healing; SRC/mitogen-activated protein kinase kinase/extracellular signal-
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