三七总皂苷对肛瘘术后大鼠创面愈合的影响及机制

王鑫民; 刘亚坤; 李刚; 刘娟; 徐会志; 张靖杰; 李民路; 牛静亚; 张丙贵

doi:10.6039/j.issn.1001-0408.2024.06.10

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三七总皂苷对肛瘘术后大鼠创面愈合的影响及机制

药学研究 | 更新时间：2024-04-09

- 三七总皂苷对肛瘘术后大鼠创面愈合的影响及机制
- Effect and mechanism of Panax notoginseng saponins on wound healing after anal fistula surgery in rats
- 中国药房 2024年35卷第6期页码：695-700
- 作者机构：
  
  1.河北中医药大学研究生学院，石家庄　050200
  2.河北省第八人民医院普外肛肠科，石家庄　050024
  3.石家庄市中医院肛肠科，石家庄　050011
  4.石家庄市藁城人民医院普外肝胆科，石家庄　052160
  5.河北中医药大学中西医结合临床学院，石家庄　050200
- 作者简介：
  
  医师，硕士研究生。研究方向：肛肠疾病诊治。 E-mail：842710813@qq.com
  主任医师，博士。研究方向：肛肠疾病诊治。E-mail：binggui7183@163.com
- 基金信息：
  
  河北省中医药管理局2019年度中医药类科研计划课题(2019175)
- DOI：10.6039/j.issn.1001-0408.2024.06.10
  中图分类号： R285.5;R965
- 纸质出版日期：2024-03-30，
  
  收稿日期：2023-08-31，
  
  修回日期：2024-01-23，
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王鑫民,刘亚坤,李刚等.三七总皂苷对肛瘘术后大鼠创面愈合的影响及机制 ^Δ[J].中国药房,2024,35(06):695-700.

WANG Xinmin,LIU Yakun,LI Gang,et al.Effect and mechanism of Panax notoginseng saponins on wound healing after anal fistula surgery in rats[J].ZHONGGUO YAOFANG,2024,35(06):695-700.
王鑫民,刘亚坤,李刚等.三七总皂苷对肛瘘术后大鼠创面愈合的影响及机制 ^Δ[J].中国药房,2024,35(06):695-700. DOI： 10.6039/j.issn.1001-0408.2024.06.10.

WANG Xinmin,LIU Yakun,LI Gang,et al.Effect and mechanism of Panax notoginseng saponins on wound healing after anal fistula surgery in rats[J].ZHONGGUO YAOFANG,2024,35(06):695-700. DOI： 10.6039/j.issn.1001-0408.2024.06.10.

摘要

目的

探究三七总皂苷（PNS）调节缺氧诱导因子1α（HIF-1α）/血管内皮生长因子（VEGF）/血管内皮生长因子受体2（VEGFR2）信号通路对肛瘘术后大鼠创面愈合的影响及潜在机制。

方法

以SD大鼠为对象，采用大肠埃希菌液感染创面的方法复制肛瘘术后大鼠模型，并将其随机分为模型组，PNS低、高剂量组（15、30 mg/cm

），PNS高剂量+2-甲氧基雌二醇（2ME2）组（PNS 30 mg/cm

+HIF-1α抑制剂2ME2 4 mg/kg），每组10只；另选10只正常大鼠，仅进行背部脱毛处理，作为对照组。各药物组大鼠肌内或（和）腹腔注射相应药液，每天1次，持续3周。末次给药后，检测各组大鼠的创面愈合率（对照组除外），创面组织微血管密度（MVD）和胶原蛋白Ⅰ（collagen Ⅰ）、纤维连接蛋白（FN）阳性表达情况，血清中血管生成相关因子[VEGF、血管生成素Ⅰ（Ang-Ⅰ）、Ang-Ⅱ]水平和血清、创面组织中炎症因子[白细胞介素6（IL-6）、IL-2]

水平，以及创面组织中HIF-1α/VEGF/VEGFR2信号通路相关蛋白的表达情况。

结果

模型组大鼠创面组织MVD及collagen Ⅰ、FN表达水平，血清及创面组织中IL-6、IL-2水平均较对照组显著升高（

＜0.05），血清中VEGF、Ang-Ⅰ、Ang-Ⅱ水平均较对照组显著降低（

＜0.05）。PNS低、高剂量组大鼠创面愈合率，创面组织MVD，血清中VEGF、Ang-Ⅰ、Ang-Ⅱ水平，创面组织中collagen Ⅰ、FN表达水平和HIF-1α、VEGF、VEGFR2蛋白的表达水平均较模型组显著升高（

＜0.05），血清及创面组织中IL-6、IL-2水平均较模型组显著降低（

＜0.05），且高剂量PNS的作用更强（

＜0.05）；2ME2可减弱PNS对肛瘘术后大鼠上述指标的改善作用（

＜0.05）。

结论

PNS可促进血管生成相关因子产生并抑制促炎因子生成，从而促进肛瘘术后大鼠创面的愈合，上述作用与激活HIF-1α/VEGF/VEGFR2信号通路有关。

Abstract

OBJECTIVE

To investigate the effect and mechanism of

Panax notoginseng

saponins （PNS） on wound healing after anal fistula surgery in rats by regulating the hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF）/vascular endothelial growth factor receptor-2 （VEGFR2） signaling pathway.

METHODS

SD rats were selected to establish a postoperative rat model of anal fistula by infecting wound with

Escherichia coli

. The model rats were randomly grouped into model group， PNS low-dose and high-dose groups （15， 30 mg/cm

）， high-dose of PNS+2-methoxyestradiol （2ME2） group （PNS 30 mg/cm

+HIF-1α inhibitor 2ME2 4 mg/kg）， with 10 rats in each group. Another 10 normal rats were selected for back hair removal treatment as the control group. Each drug group was injected with the corresponding drug solution intramuscularly or （and） intraperitoneally， once a day， for 3 weeks. After the last administration， the wound healing rate （excluding the control group）， microvascular density （MVD）， the expression of collagen Ⅰ and fibronectin （FN） in the wound tissue were detected in each group； the levels of angiogenic factors [VEGF， angiopoietin-Ⅰ （Ang-Ⅰ）， Ang-Ⅱ] in serum， the levels of inflammatory factors [interleukin-6 （IL-6） and IL-2]

in serum and wound tissue as well as the expressions of the related proteins of HIF-1α/VEGF/VEGFR2 signaling pathway in the wound tissue of rats were also detected in each group.

RESULTS

The MVD， the expression of collagen Ⅰ and FN in the wound tissue， and the levels of IL-6 and IL-2 in serum and wound tissue of rats increased significantly in the model group， compared to the control group （

＜0.05）， while the serum levels of VEGF， Ang-Ⅰ and Ang-Ⅱ decreased significantly （

＜0.05）. The wound healing rate， the MVD in wound tissue， the serum levels of VEGF， Ang-Ⅰ and Ang-Ⅱ， the expressions of collagen Ⅰ and FN in the wound tissue， and protein expressions of HIF-1α， VEGF and VEGFR2 in the PNS low-dose and high-dose groups increased significantly， compared to the model group （

＜0.05）， while the levels of IL-6 and IL-2 in serum and wound tissue decreased significantly （

＜0.05）； the high-dose PNS had a stronger effect （

＜0.05）. 2ME2 could weaken the effect of PNS on above indicators of rats after anal fistula surgery （

＜0.05）.

CONCLUSIONS

PNS can promote the production of angiogenic factors and inhibit the production of pro-inflammatory factors， thereby promoting wound healing in rats after anal fistula surgery. The above effects are related to the activation of HIF-1α/VEGF/VEGFR2 signaling pathway.

关键词

三七总皂苷肛瘘缺氧诱导因子1α/血管内皮生长因子/血管内皮生长因子受体2信号通路创面愈合

Keywords

anal fistulaHIF-1α/VEGF/VEGFR2 signaling pathwaywound healing

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