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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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          刘亚坤    1, 2* ,李 刚 ,颜 娟 ,徐会志 ,吴彦江 ,尤 帅 ,牛静亚 ,李洪健 ,张丙贵 (1.河北中医药大学研究
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          生学院,石家庄 050200;2.石家庄市中医院肛肠科,石家庄 050011;3.河北北方学院附属第一医院药学部,
          河北 张家口 075000;4.河北省第八人民医院普外肛肠科,石家庄 050024)
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2023)16-1967-05
          DOI  10.6039/j.issn.1001-0408.2023.16.09
          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(40 mg/kg)、PTE高剂量组(80 mg/kg)和PTE高剂量+PP2组(80 mg/kg的PTE+2 mg/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14 d。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。
          关键词  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

          Effects and mechanism of pterostilbene on wound healing in diabetic skin ulcer model rats
          LIU Yakun ,LI Gang ,YAN Juan ,XU Huizhi ,WU Yanjiang ,YOU Shuai ,NIU Jingya ,LI Hongjian ,
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          ZHANG Binggui  1, 4 (1.  Clinical  College  of  Integrated  Traditional  Chinese  and  Western  Medicine,  Hebei
          University  of  Traditional  Chinese  Medicine,  Shijiazhuang  050200,  China;2.  Dept.  of  Anorectal,  Shijiazhuang
          Hospital  of  Traditional  Chinese  Medicine,  Shijiazhuang  050011,  China;3.  Dept.  of  Pharmacy,  the  First
          Affiliated  Hospital  of  Hebei  North  University,  Hebei  Zhangjiakou  075000,  China;4.  Dept.  of  General
          Anorectal, the Eighth People’s Hospital of Hebei Province, Shijiazhuang 050024, China)
          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
             Δ 基金项目 河北省中医药管理局2019年度中医药类科研计划课
                                                             decreased significantly (P<0.05), while serum contents of IL-
          题(No.2019175)                                      1β,  IL-6  and  TNF- α  were  increased  significantly (P<0.05);
             *第一作者 主治医师,硕士研究生。研究方向:慢性难愈性创面。
                                                             there  was  obvious  infiltration  of  inflammatory  cells  in  the
          E-mail:1299041360@qq.com
             # 通信作者 主任医师,博士。研究方向:慢性难愈性创面。E-                  wound  granulation  tissue,  and  the  number  of  new  blood
          mail:binggui7183@163.com                           vessels decreased. Compared with model group, above indexes


          中国药房  2023年第34卷第16期                                              China Pharmacy  2023 Vol. 34  No. 16    · 1967 ·
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