Effect of cinnamaldehyde on Bax/Bak and apoptosis of vascular endothelial cells in diabetic ulcers

JIN Zheyu; XIE Chenlei; FAN Xinqi; YANG Shu; DONG Ruiyi; BAI Yanyu; DING Yarong; ZHOU Zhongzhi; CHEN Li

doi:10.16016/j.2097-0927.202506009

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Effect of cinnamaldehyde on Bax/Bak and apoptosis of vascular endothelial cells in diabetic ulcers

Basic Medicine | 更新时间：2025-11-13

- Effect of cinnamaldehyde on Bax/Bak and apoptosis of vascular endothelial cells in diabetic ulcers
- Journal of Army Medical University Vol. 47, Issue 21, Pages: 2678-2687(2025)
- 作者机构：
  
  1.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，湖南长沙
  2.湖南中医药大学第一附属医院烧伤疮疡整形科，湖南长沙
- 作者简介：
  
  CHEN Li， E-mail： 1224909171@qq.com
- 基金信息：
  
  the Project of Key Disciplines and Applied Characteristic Disciplines Construction of Hunan Province during the 14th Five-Year Plan Period （Xiangjiao Tong ［2022］ No.351）, the Project of Hunan Provincial Key Laboratory, Department of Science and Technology of Hunan Province(湘教通〔2022〕351号);the Key R&D Program of Hainan Provincial Department of Science and Technology(2023TP1018);the Scientific Research Project of Education Department of Hunan Province(ZDYF2023SHFZ123);the Traditional Chinese Medicine Research Project of Hunan Province(23A0294);the Young Backbone Talent Program for Medical Disciplines, Health Commission of Hunan Province, the Backbone Talent Program for Traditional Chinese Medicine of Hunan Province during the 14th Five-Year Plan Period(A2024004)
- DOI：10.16016/j.2097-0927.202506009
  CLC： R285.5;R587.2;R6332.1
- Received：04 June 2025，
  
  Revised：2025-10-27，
  
  Accepted：27 October 2025，
  
  Published：15 November 2025
- 稿件说明：
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金哲羽，谢晨磊，范心琪，等.肉桂醛对糖尿病溃疡血管内皮细胞Bax/Bak和凋亡的影响［J］.陆军军医大学学报，2025，47（21）：2678-2687.DOI：10.16016/j.2097-0927.202506009.

JIN Z Y，XIE C L，FAN X Q，et al.Effect of cinnamaldehyde on Bax/Bak and apoptosis of vascular endothelial cells in diabetic ulcers［J］.J Army Med Univ，2025，47（21）：2678-2687.DOI：10.16016/j.2097-0927.202506009.
金哲羽，谢晨磊，范心琪，等.肉桂醛对糖尿病溃疡血管内皮细胞Bax/Bak和凋亡的影响［J］.陆军军医大学学报，2025，47（21）：2678-2687.DOI：10.16016/j.2097-0927.202506009. DOI：

JIN Z Y，XIE C L，FAN X Q，et al.Effect of cinnamaldehyde on Bax/Bak and apoptosis of vascular endothelial cells in diabetic ulcers［J］.J Army Med Univ，2025，47（21）：2678-2687.DOI：10.16016/j.2097-0927.202506009. DOI：

摘要

目的

探究肉桂醛（cinnamic aldehyde，CA）对糖尿病溃疡创面组织血管内皮细胞中Bcl-2相关X蛋白（Bcl-2-associated X protein，Bax）和Bcl-2拮抗因子（Bcl-2 homologous antagonist/killer，Bak）及细胞凋亡的影响。

方法

①将48只5周龄健康SPF级雄性SD大鼠（体质量180~220 g）采用随机数字法选取12只作为空白（Con）组，剩余36只作为糖尿病（Diabetes）组。对Diabetes组进行50 mg/kg的STZ-柠檬酸钠混合液腹腔注射联合高脂饲料喂养建立糖尿病大鼠模型。将Diabetes组采用随机数字法分为（

=12）：模型（Model）组、CA组和贝复新（rb-bFGF）组，Con组和Model组创面常规消毒后予以生理盐水涂抹，CA组涂抹含4 µmol/L CA的聚乙二醇400（PEG 400）凝胶，rb-bFGF组创面涂抹贝复新凝胶。记录大鼠糖尿病造模后血糖监测情况，分别于干预后第3、7、14天计算各组创面愈合率，干预后第14天HE染色监测创面组织病理变化和Western blot法检测Bax、Bak表达水平。②采用175 mmol/L高糖干预人脐静脉血管内皮细胞（EA.hy926）48 h，建立细胞高糖损伤模型。实验细胞分为正常（Cell-Con）组、模型（Cell-Model）组、CA（Cell-CA）组。通过划痕实验检测血管内皮细胞迁移能力，成管实验检测血管内皮细胞形成血管的能力，运用免疫荧光技术分析Bax、Bak荧光蛋白的表达水平，运用TUNEL染色检测血管内皮细胞凋亡水平。

结果

①动物实验结果显示，造模后Diabetes组大鼠血糖值明显高于Con组（

0.05）。干预后第7、14天，与Con组相比，Model组创面愈合率显著下降（

0.05）。干预后第14天，Con组全损皮层完成上皮化，而Model组溃疡处炎症细胞密集浸润，新生血管罕见，创面表面表现为持续液体渗出，并伴有炎症反应，Bax、Bak表达显著上升（

0.05）。与Model组相比，CA组和rb-bFGF组上皮化进程明显，肉芽组织趋于成熟，愈合情况良好，创面愈合率显著上升（

0.05），CA组Bax、Bak表达显著下降（

0.05），rb-bFGF组Bax、Bak表达显著下降（

0.05）。②细胞实验结果显示，与Cell-Con组相比，Cell-Model组血管内皮细胞迁移活力、成管能力均显著下降（

0.05），Bax、Bak荧光蛋白表达水平上升（

0.05），细胞凋亡明显增加（

0.05）。与Cell-Model组相比，Cell-CA组血管内皮细胞迁移活力、成管能力均显著上升（

0.05），Bax、Bak荧光蛋白表达水平降低（

0.05），细胞凋亡明显减少（

0.05）。

结论

CA能够抑制凋亡相关蛋白Bax、Bak的表达，促进血管内皮细胞迁移与成管，抑制高糖下的血管内皮细胞凋亡，可能是促进糖尿病溃疡大鼠伤口愈合的重要原因。

Abstract

Objective

To investigate the effects of cinnamic aldehyde (CA) on Bcl-2-associated X protein (Bax) and Bcl-2 homologous antagonist/killer (Bak) in vascular endothelial cells of diabetic ulcer wound tissues

as well as on cell apoptosis.

Methods

① Forty-eight healthy SPF-grade male SD rats (5 weeks old

weighing 180~220 g) were randomly assigned to a control group (12 rats) and a diabetes group (36 rats). The diabetic model was established with an intraperitoneal injection of 50 mg/kg STZ-citrate sodium solution and high-fat diet feeding. The diabetes group was further randomly divided into Model group

CA group

and the rb-bFGF group

with 12 animals in each group. Wounds in the Con and Model groups were disinfected and topically treated with normal saline

CA group received topical application of 4 µmol/L CA in PEG 400 gel

and those of the rb-bFGF group were treated with bevacizumab gel. The wound healing rate of each group was calculated at 3

7 and 14 d after intervention. At 14 d after intervention

pathological changes in the wounds were observed with HE staining

and the expression levels of Bax and Bak were detected by Western blotting. ② Human umbilical vein endothelial cell line EA.hy926 was treated with 175 mmol/L glucose for 48 h to establish a cell model of high glucose injury. The experimental cells were divided into control group

model group and CA treatment group. Cell scratch test and tube formation test were performed respectively to determine the migration ability and angiogenesis of the cells. The expression levels of Bax and Bak was detected with immunofluorescence assay

and cell apoptosis was detected by TUNEL staining.

Results

①The diabetic rats in the Model group exhibited significantly higher blood glucose level (

0.05)

declined wound healing rate at 7 and 14 d after intervention (

0.05)

and enhanced expression levels of Bax and Bak (

0.05) when compared with the control group. Pathological observation revealed that

at 14 d after intervention

accompanied with inflammatory reactions

dense infiltration of inflammatory cells

fewer new blood vessels

and continuous fluid exudation in the wound were observed in the Model group

but the control group presented complete epithelialization in full-thickness skin. Compared with the conditions in the Model group

both CA and rb-bFGF treatment improved the epithelialization process

with mature granulation tissues

showing good healing condition

promoted wound healing rate (

0.05)

and decreased the expression levels of Bax and Bak (

0.05). ② The results of cell experiments showed that the cells of the model group showed significantly reduced migration ability and tube formation ability (

0.05)

reduced protein levels of Bax and Bak (

0.05)

and lower apoptotic rate (

0.05) when compared with the cells in the model group.

Conclusion

CA can inhibit the expression of apoptosis-related proteins Bax and Bak

promote the migration and tube formation of vascular endothelial cells

and inhibit the cell apoptosis under high glucose condition

which may be an important reason for its promoting wound healing in diabetic ulcer rats.

关键词

Keywords

references

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