Topical administration of cinnamic aldehyde accelerates wound healing in diabetic mice by activation of Nrf2 pathway

Leiqin CAI; Wenjie LI; Min LONG; Hongting ZHENG

doi:10.16016/j.1000-5404.201704153

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Topical administration of cinnamic aldehyde accelerates wound healing in diabetic mice by activation of Nrf2 pathway

Basic Medicine | 更新时间：2026-01-09

- Topical administration of cinnamic aldehyde accelerates wound healing in diabetic mice by activation of Nrf2 pathway
- Journal of Third Military Medical University Vol. 39, Issue 19, Pages: 1906-1912(2017)
- 作者机构：
  
  400037 重庆, 第三军医大学新桥医院内分泌科
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81471039);the National Natural Science Foundation of Young Scholars of China(81500647);the Project of Basic Science and Frontier Technology of Chongqing(CSTC2016jcyjA1584);the Project of Diabetic Research for Young Doctors(2015)
- DOI：10.16016/j.1000-5404.201704153
  CLC： R587.2;R969;R977.6
- Received：05 April 2017，
  
  Revised：2017-07-03，
  
  Published：15 October 2017
- 稿件说明：
移动端阅览
Leiqin CAI, Wenjie LI, Min LONG, et al. Topical administration of cinnamic aldehyde accelerates wound healing in diabetic mice by activation of Nrf2 pathway[J]. Journal of Third Military Medical University, 2017, 39(19): 1906-1912.
DOI：

Leiqin CAI, Wenjie LI, Min LONG, et al. Topical administration of cinnamic aldehyde accelerates wound healing in diabetic mice by activation of Nrf2 pathway[J]. Journal of Third Military Medical University, 2017, 39(19): 1906-1912. DOI： 10.16016/j.1000-5404.201704153.

摘要

目的

探讨局部应用肉桂醛(cinnamic aldehyde

CA)对糖尿病小鼠创口愈合的影响及其机制。

方法

8周龄Nrf2野生型(Nrf2

+/+

)和Nrf2敲除型(Nrf2

-/-

)雄性SKH-1无毛小鼠各8只

持续5 d腹腔注射链脲霉素(streptozotocin

STZ

50 mg/kg)

建立糖尿病小鼠模型。采用随机数字表法分为:① Nrf2

+/+

鼠对照组(Nrf2

+/+

Veh组); ② Nrf2

+/+

鼠CA治疗组(Nrf2

+/+

CA组); ③ Nrf2

-/-

鼠Veh组(Nrf2

-/-

Veh组); ④ Nrf2

-/-

鼠CA组(Nrf2

-/-

CA组)(

=4)。STZ注射后第4周，在小鼠背部建立直径6 mm的全层皮肤切除创口。Nrf2

+/+

CA组和Nrf2

-/-

CA组术后当日开始局部应用20 μL含4 μmol/L CA的聚乙二醇400(polyethylene glycol400

PEG400)

每隔1天干预直至第14天

收集创缘处皮肤

Nrf2

+/+

Veh组和Nrf2

-/-

Veh组采用20 μL PEG400(Vehicle

Veh)局部应用作为空白对照。术后2周内每隔1天监测皮肤创口愈合面积评估愈合速率。免疫组化染色对比各组创缘处皮肤组织Nrf2蛋白、下游靶蛋白HO-1和氧化应激损伤相关指标8-oxo-dG的表达水平。

结果

局部应用CA明显加速Nrf2

+/+

糖尿病小鼠创口愈合(

0.05)

但是并不影响Nrf2

-/-

糖尿病小鼠创口愈合(

0.05)。免疫组化示Nrf2

+/+

糖尿病溃疡小鼠局部应用CA后

其创缘皮肤Nrf2的表达水平[(2.42±0.29)

(7.42±0.73)

0.05

]

和下游靶蛋白HO-1的表达水平[(5.92±0.36)

(8.88±0.53)

0.05

]

显著增强

8-oxo-dG的表达水平则明显减少[(9.46±0.28)

(8.46±0.23)

0.05

]

。Nrf2

-/-

糖尿病小鼠创口局部外用CA后

其创缘处皮肤Nrf2、HO-1及8-oxo-dG的表达水平与Nrf2

-/-

Veh组相比并无明显变化。

结论

局部应用CA通过激活糖尿病小鼠皮肤组织Nrf2通路

减轻氧化应激损伤

从而促进糖尿病创口愈合。

Abstract

Objective

To determine the effect of topical administration of cinnamic aldehyde (CA) on wound healing in diabetic mice

and investigate the underlying mechanism.

Methods

A total of 8 Nrf2

+/+

and 8 Nrf2

-/-

male hairless SKH-1 mice (8 weeks old) were intraperitoneally injected with streptozotocin (STZ

50 mg/kg) for 5 consecutive days to establish diabetic model. The mice were randomly divided into 4 groups: control group of Nrf2

+/+

mice (Nrf2

+/+

Veh)

CA treatment group of Nrf2

+/+

mice (Nrf2

+/+

CA)

control group of Nrf2

-/-

mice (Nrf2

-/-

Veh)

and CA treatment group of Nrf2

-/-

mice (Nrf2

-/-

CA) (

=4 for each group). In 4 weeks after STZ injection

2 full-thickness wounds (6 mm in size) were made on the back of the mice. From the day after surgery

Nrf2

+/+

CA and Nrf2

-/-

CA groups received topical administration with 20 μL 4 μmol/L CA diluted by polyethylene glycol 400 (PEG 400) every other day until skin tissues were harvested at the 14th day post-surgery

and Nrf2

+/+

Veh and Nrf2

-/-

Veh groups were given 20 μL PEG 400 as control. Meanwhile

the wound closure rates were monitored and assessed in 2 weeks post-surgery. The expression levels of Nrf2

downstream target protein HO-1

and 8-oxo-2'-deoxyguanosine (8-oxo-dG

a sensitive parameter for oxidative stress) in the skin of each group were assessed by immunohistochemistry.

Results

Topical administration of CA significantly accelerated the wound healing of Nrf2

+/+

diabetic mice (

0.05)

but had no such effect on the Nrf2

-/-

CA group (

0.05). Moreover

the expression levels of Nrf2 (2.42±0.29

7.42±0.73

0.05) and HO-1 (5.92±0.36

8.88±0.53

0.05) were increased

while the level of 8-oxo-dG (9.46±0.28

8.46±0.23

0.05) was decreased at the wound site after CA treatment in Nrf2

+/+

diabetic mice. However

in the Nrf2

-/-

diabetic mice

CA treatment showed no effect on the expression levels of Nrf2

HO-1 and 8-oxo-dG.

Conclusion

Topically application of CA promotes diabetic wound healing

via

activation of Nrf2 pathway and alleviation of oxidative damage.

关键词

Keywords

references

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