负载姜黄素的犬脂肪间充质干细胞来源外泌体对皮肤损伤愈合的效果及机制研究

doi:10.11843/j.issn.0366-6964.2025.08.041

摘要/Abstract

摘要：

本研究旨在探讨负载姜黄素(curcumin, CUR)的犬脂肪间充质干细胞来源的外泌体(exosomes derived from adipose mesenchymal stem cells, cADMSC-EXO)对皮肤损伤修复的效果及可行性。将小鼠和犬随机分为四组：对照组(CON)、外泌体治疗组(EXO)、姜黄素治疗组(CUR)和负载姜黄素的外泌体组(EXO-CUR)。制作直径1 cm(小鼠)和1.5 cm(犬)的背部全层皮肤损伤模型，并在第1、3、5、7、9天进行皮下注射。结果发现，相较于CON组和其他单独治疗组，负载CUR的cADMSC-EXO能够加速小鼠和犬皮肤损伤模型的伤口愈合，显著促进皮肤组织结构的恢复。其通过上调皮肤愈合相关基因(VEGFA、FGF2)和抗炎因子IL-10的表达，促进损伤修复；同时下调疤痕相关基因(SOX9、TGF-β1、Twist1)并上调TGF-β3的表达，减少瘢痕形成。此外，小鼠血清中皮肤愈合因子(VEGF、FGF2)水平升高，氧化应激相关因子ROS减少，GSH水平增加；炎症因子(IL-1β、TNF-α)含量降低。负载CUR的cADMSC-EXO能够有效促进皮肤损伤的修复，且相较于单独使用CUR或者EXO效果更佳。

关键词: 皮肤损伤, 脂肪间充质干细胞, 外泌体, 姜黄素, 小鼠, 犬

Abstract:

This study aimed to investigate the effects and feasibility of curcumin (CUR)-loaded exosomes derived from canine adipose mesenchymal stem cells (cADMSC-EXO) on skin wound healing. Mice and dogs were randomly divided into four groups: control group (CON), exosome treatment group (EXO), curcumin treatment group (CUR), and curcumin-loaded exosome group (EXO-CUR). For the wound model, a full-thickness skin wound with a diameter of 1 cm was created on the back of each mouse, and a 1.5 cm full-thickness wound on the back of each dog. Subcutaneous injections were administered on days 1, 3, 5, 7, and 9 for both species. The results showed that curcumin-loaded cADMSC-EXO significantly accelerated wound healing in both mouse and canine skin injury models, promoting the structural restoration of skin tissue. EXO-CUR enhanced wound repair by upregulating the expression of wound healing-related genes (VEGFA, FGF2) and the anti-inflammatory factor IL-10, while downregulating scar-related genes (SOX9, TGF-β1, Twist1) and upregulating TGF-β3, thereby reducing scar formation. Additionally, in mouse serum, levels of wound healing factors (VEGF, FGF2) increased, oxidative stress-related factor ROS decreased, and GSH levels rose. Furthermore, inflammatory factors (IL-1β, TNF-α) were reduced. These results indicate that cADMSC-EXO loaded with CUR can effectively promote the repair of skin damage, and is more effective than using CUR or EXO alone.

Key words: skin injury, adipose-derived mesenchymal stem cells, exosomes, curcumin, mice, canine

中图分类号:

S857.5

王苗, 伏庭书, 陈梦炜, 周宏达, 柏小楠, 马保华, 彭莎. 负载姜黄素的犬脂肪间充质干细胞来源外泌体对皮肤损伤愈合的效果及机制研究[J]. 畜牧兽医学报, 2025, 56(8): 4042-4052.

WANG Miao, FU Tingshu, CHEN Mengwei, ZHOU Hongda, BAI Xiaonan, MA Baohua, PENG Sha. Study on the Repairing Effect of Exosomes Derived from Adipose Mesenchymal Stem Cells Loaded with Curcumin on Skin Injury[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(8): 4042-4052.

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基因名称 Gene name	上游引物(5′→3′) Forward primers	下游引物(5′→3′) Reverse primers
Canine-VEGFA	CTATGGCAGGAGGAGAGCAC	CCCTATGTGCTGGCCTTGAT
Canine-FGF2	CGATCCCCACGTCAAATTGC	CTTTCTGCCCAGGTCCTGTT
Canine-Wnt4	TCCTGCGAGGTAAAGACGTG	GCAGCCGTCAATGGCTTTAG
Canine-GAPDH	TGTCATCAACGGGAAGTCCA	TCTCATGGTTCACGCCCATC
MOUSE-VEGFA	TCTTCCAGGAGTACCCCGAC	GGGATTTCTTGCGCTTTCGT
MOUSE-FGF2	GGCTGCTGGCTTCTAAGTGT	GTCCCGTTTTGGATCCGAGT
MOUSE-TGF-β1	GTGGAAATCAACGGGATCAGC	AGTTGGTATCCAGGGCTCTC
MOUSE-SOX9	CACAAGAAAGACCACCCCGA	GGACCCTGAGATTGCCCAGA
MOUSE-TGF-β3	GCACTTTACAACAGCACCCG	GACGGCCAGTTCATTGTGC
MOUSE-IL-10	GTAGAAGTGATGCCCCAGGC	GACACCTTGGTCTTGGAGCTTATT
MOUSE-Twist1	GGCCGGAGACCTAGATGTCATT	CTGGGAATCTCTGTCCACGG
MOUSE-GADPH	GGAGAGTGTTTCCTCGTCCC	TTCCCATTCTCGGCCTTGAC
MOUSE-COL1A1	AGGAGAGGGGAGAGGAGGAG	TGAAGAGAGAGGAAGGAGAGG
MOUSE-COL3A1	CAGGGTCTGAGGAGAGAGGG	AGGAAGTCTGGGAGAGAGGA
MOUSE-MMP-2	TCCACCACACATGGAAGAG	AGGAGAGAGGAGAGGAAGGA
MOUSE-HAS1	CTGGAGGAAGGAAGGAGGA	AGGAGAGAGGAGAGAGAGGA
MOUSE-LAMA4	CTGGAGGAAGGAAGGAGGA	AGGAGAGAGGAGAGAGAGGA

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