Effect of <italic style="font-style: italic">Wenyang Shengji Ointment</italic> （温阳生肌膏） on MGO Content and HIF-1a/VEGF Pathway in Wound Tissue of Diabetic Wound Model Rats with <italic style="font-style: italic">Yin</italic> Syndrome

HUANG Xinyu; CHEN Li; DING Yarong; WANG Jun; FENG Shuihua; ZHOU Zhongzhi

doi:10.13288/j.11-2166/r.2025.04.010

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Effect of Wenyang Shengji Ointment （温阳生肌膏） on MGO Content and HIF-1a/VEGF Pathway in Wound Tissue of Diabetic Wound Model Rats with Yin Syndrome

更新时间：2025-02-18

- Effect of Wenyang Shengji Ointment （温阳生肌膏） on MGO Content and HIF-1a/VEGF Pathway in Wound Tissue of Diabetic Wound Model Rats with Yin Syndrome
- Journal of Traditional Chinese Medicine Vol. 66, Issue 4, Pages: 382-389(2025)
- 作者机构：
  
  1.湖南中医药大学第一附属医院，湖南省长沙市韶山中路95号，410007
  2.湖南中医药大学第一中医临床学院
  3.湖南中医药大学血管生物学与转化医学湖南省重点实验室
  4.海南省人民医院
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2025.04.010
  CLC：
- Received：08 September 2024，
  
  Revised：2024-10-30，
  
  Published：17 February 2025
- 稿件说明：
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黄新宇,陈丽,丁雅容等.温阳生肌膏对糖尿病阴证创面模型大鼠创面组织甲基乙二醛含量及HIF-1α/VEGF通路的影响[J].中医杂志,2025,66(04):382-389.

HUANG Xinyu,CHEN Li,DING Yarong,et al.Effect of Wenyang Shengji Ointment （温阳生肌膏） on MGO Content and HIF-1a/VEGF Pathway in Wound Tissue of Diabetic Wound Model Rats with Yin Syndrome[J].Journal of Traditional Chinese Medicine,2025,66(04):382-389.
黄新宇,陈丽,丁雅容等.温阳生肌膏对糖尿病阴证创面模型大鼠创面组织甲基乙二醛含量及HIF-1α/VEGF通路的影响[J].中医杂志,2025,66(04):382-389. DOI： 10.13288/j.11-2166/r.2025.04.010.

HUANG Xinyu,CHEN Li,DING Yarong,et al.Effect of Wenyang Shengji Ointment （温阳生肌膏） on MGO Content and HIF-1a/VEGF Pathway in Wound Tissue of Diabetic Wound Model Rats with Yin Syndrome[J].Journal of Traditional Chinese Medicine,2025,66(04):382-389. DOI： 10.13288/j.11-2166/r.2025.04.010.

摘要

目的

探讨温阳生肌膏治疗糖尿病阴证创面的可能作用机制。

方法

24只SD大鼠随机分为正常组6只及造模组18只。造模组大鼠以高脂饲料喂养14天后联合链脲霉素腹腔注射制备糖尿病模型，以糖皮质激素肌肉注射后于大鼠背部手术形成全层皮肤缺损进而建立糖尿病阴证创面大鼠模型；正常组普通饲料喂养，于大鼠背部手术形成全层皮肤缺损创面。将18只造模成功大鼠随机分为模型组、温阳生肌膏组、贝复新组各6只。温阳生肌膏组创面涂抹温阳生肌膏，贝复新组创面涂抹贝复新凝胶，正常组、模型组大鼠创面常规消毒后予生理盐水涂抹。各组均每日换药1次，共给药14天。分别在给药第0、3、7、14天记录创面愈合情况并计算第3、7、14天时创面愈合率。第14天给药后HE染色观察各组大鼠创面组织病理形态；Western Blot法检测创面组织缺氧诱导因子1α（HIF-1α）、血管内皮生长因子（VEGF）蛋白相对含量；免疫荧光法检测创面组织HIF-1α荧光强度；ELISA法检测创面组织甲基乙二醛（MGO）含量。

结果

与正常组比较，模型组大鼠给药第3、7、14天创面修复情况较差，创面愈合率降低（

＜0.01）；HE染色显示，创面组织痂皮覆盖，有炎细胞浸润，胶原排列紊乱；创面组织VEGF蛋白相对含量显著降低，HIF-1α蛋白相对含量及MGO含量显著增加（

＜0.01），HIF-1α荧光强度增强。与模型组比较，温阳生肌膏组、贝复新组给药第3、7、14天创面愈合情况较好，创面愈合率均增高（

＜0.01）；创面组织可见清晰完整的上皮层结构，炎细胞消退，肉芽组织成熟，胶原排列整齐；MGO含量均显著降低（

＜0.01）；温阳生肌膏组HIF-1α、VEGF蛋白相对含量均显著增加，而贝复新组仅VEGF蛋白相对含量增加（

＜0.05或

＜0.01）。与贝复新组比较，温阳生肌膏组创面表皮层较厚，可见粗大胶原形成，HIF-1α荧光表达明显增加，创面组织MGO含量下调，HIF-1α蛋白相对含量增高（

＜0.05）。

结论

温阳生肌膏可减少糖尿病阴证创面组织MGO堆积，激活HIF-1α/VEGF通路，可能是其促进创面愈合的机制之一。

Abstract

Objective

To investigate the possible mechanism of

Wenyang Shengji Ointment

（温阳生肌膏， WSO） in the treatment of diabetic wounds with

yin

syndrome.

Methods

A total of 24 SD rats were randomly divided into a group （n=6） and modeling group （n=18）. The modeling group rats were fed with high-fat diet for 14 days and then were injected intraperitoneally with streptozotocin to induce diabetic model. After steroid injection， full-thickness skin defects were created on the back of the rats to establish a diabetic wound with

yin

syndrome model. The normal group was fed with regular diet， and full-thickness skin defects were created surgically on the back of the rats. The 18 successfully modeled rats were further divided into three groups， the model group， the WSO group， and the

Beifuxin

（Recombinant Bovine Basic Fibroblast Growth Factor Gel， BX） group， 6 rats in each group. The WSO group was given the ointment to the wound， the

Beifuxin

group was givne BX gel， and the normal group and model group was disinfected and treated with saline. All groups had their dressings changed once daily fo

r 14 days. Wound healing was recorded on days 0， 3， 7， and 14， and the wound healing rate was calculated on day 3， 7， and 14. On day 14 after treatment， HE staining was performed to observe the pathological morphology of the wound tissue. Western Blot was used to detect the relative protein levels of hypoxia-inducible factor 1 alpha （HIF-1α） and vascular endothelial growth factor （VEGF）. Immunofluorescence was used to measure the fluorescence intensity of HIF-1α in the wound tissue， and ELISA was used to detect the methylglyoxal （MGO） content in the wound tissue.

Results

Compared with the normal group， the model group showed poor wound healing on day 3， 7， and 14， with a low wound healing rate （

＜0.01）. HE staining showed scab coverage on the wound， with inflammatory cell infiltration and disorganized collagen arrangement. The relative protein levels of VEGF were significantly reduced， while the relative protein levels of HIF-1α and the MGO content significantly increased （

＜0.01）， and the fluorescence intensity of HIF-1α was enhanced. Compared to the model group， the WSO group and

Beifuxin

group showed better wound healing on day 3， 7， and 14， with an increased wound healing rate （

＜0.01）. The wound tissue showed clear and complete epithelial structure， reduced inflammatory cells， mature granulation tissue， and organized collagen arrangement. MGO content was significantly reduced （

＜0.01）. The relative protein levels of HIF-1α and VEGF both significantly increased in the WSO group， while only VEGF increased in the

Beifuxin

group （

＜0.05 or

＜0.01）. Compared with the

Beifuxin

group， the WSO group had a thicker epidermal layer， prominent collagen formation， significantly increased HIF-1α fluorescence expression， reduced MGO content in the wound tissue， and higher relative protein levels of HIF-1α （

＜0.05）.

Conclusion

WSO can reduce the accumulation of MGO in diabetic wound tissue with

yin

syndrome and activate the HIF-1α/VEGF pathway， which could be one of the mechanisms for promoting wound healing.

关键词

Keywords

references

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The Second Hospital of Hebei Medical University

Yueyang Hospital of Shanghai University of Traditional Chinese Medicine

上海中医药大学附属岳阳中西医结合医院上海市虹口区甘沙路110号

School of Acupuncture-Moxibustion and Tuina，Guizhou University of Traditional Chinese Medicine

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⁰

Effect of Wenyang Shengji Ointment （温阳生肌膏） on MGO Content and HIF-1a/VEGF Pathway in Wound Tissue of Diabetic Wound Model Rats with Yin Syndrome

DOI：10.13288/j.11-2166/r.2025.04.010

摘要

Abstract

关键词

Keywords

references