Exploring Effect and Mechanism of Astragaloside on Repair and Healing in Chronic Non-healing Wound Rat Model Based on SIRT1 and PI3K/Akt Signaling Pathway

CUI Mengdi; GAO Jiawei; ZHU Lvqun; CHEN Guisheng; CHEN Yiliang

doi:10.13422/j.cnki.syfjx.20240116

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Exploring Effect and Mechanism of Astragaloside on Repair and Healing in Chronic Non-healing Wound Rat Model Based on SIRT1 and PI3K/Akt Signaling Pathway

更新时间：2024-02-04

- Exploring Effect and Mechanism of Astragaloside on Repair and Healing in Chronic Non-healing Wound Rat Model Based on SIRT1 and PI3K/Akt Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 30, Issue 6, Pages: 101-108(2024)
- 作者机构：
  
  1.南京中医药大学，南京 210023
  2.南京中医药大学附属南京中医院，南京 210000
  3.南京市第二医院，南京 210003
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20240116
  CLC： R284;R285;R289;R287;R22;R2-031;R33;R24
- Received：19 September 2023，
  
  Published Online：15 January 2024，
  
  Published：20 March 2024
- 稿件说明：
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崔梦迪,高加巍,朱吕群等.基于SIRT1和PI3K/Akt信号通路探讨黄芪甲苷对慢性难愈性创面大鼠模型修复愈合的影响及作用机制[J].中国实验方剂学杂志,2024,30(06):101-108.

CUI Mengdi,GAO Jiawei,ZHU Lvqun,et al.Exploring Effect and Mechanism of Astragaloside on Repair and Healing in Chronic Non-healing Wound Rat Model Based on SIRT1 and PI3K/Akt Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(06):101-108.
崔梦迪,高加巍,朱吕群等.基于SIRT1和PI3K/Akt信号通路探讨黄芪甲苷对慢性难愈性创面大鼠模型修复愈合的影响及作用机制[J].中国实验方剂学杂志,2024,30(06):101-108. DOI： 10.13422/j.cnki.syfjx.20240116.

CUI Mengdi,GAO Jiawei,ZHU Lvqun,et al.Exploring Effect and Mechanism of Astragaloside on Repair and Healing in Chronic Non-healing Wound Rat Model Based on SIRT1 and PI3K/Akt Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2024,30(06):101-108. DOI： 10.13422/j.cnki.syfjx.20240116.

摘要

目的

探讨黄芪甲苷对慢性难愈性创面修复愈合的促进作用及其机制。

方法

60只雄性SD大鼠背部构建全层皮肤缺损创面，除正常组外，其余大鼠构建难愈性创面模型，随机分为模型组、黄芪甲苷低、高剂量组、黄芪甲苷+ LY294002［磷酸肌醇3-激酶（PI3K）抑制剂］组和黄芪甲苷+EX527［沉默调节蛋白1（SIRT1）抑制剂）］组。观察各组大鼠创面造模后第2、4、6、8天的伤口面积占比；免疫荧光检测创面组织Ⅰ型胶原

1（COL1A1）和

-肌动蛋白（

-SMA）表达；苏木素-伊红（HE）染色检测创面组织病理结构；实时荧光定量聚合酶链式反应（Real-time PCR）检测创面炎症因子mRNA表达；蛋白免疫印迹法（Western blot）检测创面SIRT1/核转录因子（NF）-

B和PI3K/蛋白激酶B（Akt）信号通路相关蛋白表达。

结果

与模型组比较，黄芪甲苷低、高剂量组大鼠术后伤口面积占比均随时间逐渐降低，且黄芪甲苷高剂量组疗效更佳。与正常组比较，模型组创面组织COL1A1荧光强度降低而

-SMA表达升高；上皮组织破损严重，厚度增加，可见大量炎性细胞浸润；肿瘤坏死因子（TNF）-

、白细胞介素（IL）-1

、IL-6和诱导型一氧化氮合酶（iNOS）的mRNA表达升高；NF-

B p65、磷酸化（p）-PI3K/PI3K和p-Akt/Akt蛋白表达升高，而SIRT1表达降低（

0.05）。与模型组比较，黄芪甲苷治疗后COL1A1和

-SMA荧光强度增高；上皮细胞数量增多，厚度降低，炎性细胞减少，胶原数量增多；TNF-

、IL-1

、IL-6和iNOS的mRNA表达降低；NF-

B p65、p-PI3K/PI3K和p-Akt/Akt蛋白表达降低，SIRT1升高，且高剂量组效果更佳（

0.05）。与黄芪甲苷高剂量组比较，LY294002和EX527抑制PI3K/Akt和SIRT1通路可阻止黄芪甲苷对慢性难愈性创面的治疗效力。

结论

黄芪甲苷外用对大鼠慢性难愈性创面愈合有明显促进作用，其机制可能与激活PI3K/Akt通路和SIRT1/NF-

B通路有关。

Abstract

Objective

To investigate the promotional effect of astragaloside on the repair and healing of chronic non-healing wounds and its mechanism.

Method

A total of 60 male SD rats were constructed with full-layer skin defect wounds on the back， and except for the control （Con） group， the rest were constructed with non-healing wounds， which were then randomly divided into the sham-operation （sham） group， the low-dose astragaloside group， the high-dose astragaloside group， the astragaloside + LY294002 ［phosphatidylinositol 3-kinase （PI3K） inhibitor］ group， and the astragaloside + EX527 ［silencing regulatory protein 1 （SIRT1） inhibitor］ group. The percentage of wound area in each group was observed on the 2nd， 4th， 6th， and 8th days after wound molding. Collagen type Ⅰ alpha 1 （COL1A1） and alpha smooth muscle actin （

-SMA） expressions in the wound tissue were detected by immunofluorescence. Hematoxylin and eosin （HE） staining was performed to determine the pathological structure of the wound. The mRNA expression of inflammatory factors in the wound was measured by real-time polymerase chain reaction （Real-time PCR）， and the expression of proteins related to the SIRT1/ nuclear factor （NF）-

B and PI3K/protein kinase B （Akt） signaling pathways in the wound was tested by Western blot.

Result

Compared with the sham group， the percentage of postoperative wound area of rats in both low-dose and high-dose astragaloside groups gradually decreased with time， and the efficacy of the high-dose astragaloside group was better. Compared with the Con group， the fluorescence intensity of COL1A1 in wound tissue of the sham group decreased， while the expression of

-SMA increased. The epithelial tissue was severely damaged， with an increase in the thickness， and a large number of inflammatory cells were seen in the infiltration. The mRNA expression of tumor necrosis factor （TNF）-

， interleukin （IL）-1

， IL-6， and inducible nitric oxide synthase （iNOS） was elevated. The protein expression of NF-

B p65， p-PI3K/PI3K， and p-Akt/Akt was elevated， while SIRT1 expression was decreased （

0.05）. Compared with the sham group， the fluorescence intensity of COL1A1 and

-SMA increased after astragaloside treatment. The number of epithelial cells increased， and the thickness decreased. The inflammatory cells decreased， and the amount of collagen increased. The mRNA expression of TNF-

， IL-1

， IL-6， and iNOS was decreased， and the protein expression of NF-

B p65， p-PI3K/PI3K， and p-Akt/Akt was decreased. SIRT1 was elevated， and the effect was better in the high-dose astragaloside group （

0.05）. Compared with the high-dose astragaloside group， inhibition of the PI3K/Akt and SIRT1 pathways by LY294002 and EX527 prevented the therapeutic efficacy of astragaloside on chronic non-healing wounds.

Conclusion

The topical application of astragaloside significantly promotes the healing of chronic non-healing wounds in rats， and the mechanism may be related to the activation of the PI3K/Akt pathway and the SIRT1/NF-

B pathway.

关键词

Keywords

references

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