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石榴皮提取物通过调节VEGF-A和TGF-β1对二度烧伤创面愈合的促进作用

Promoting effect of pomegranate peel extract on second-degree burn wound-healing through VEGF-A and TGF-β1 regulation.

作者信息

Zhang Li, Yang Renhua, Hu Yangyang, Yang Yan, Zhang Xiaochao, He Bo, Shen Zhiqiang, Yang JianYu, Chen Peng

机构信息

School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, 1168 West Chunrong Road, Kunming, Yunnan 650500, China.

School of Basic Medical Science, Kunming Medical University, 1168 West Chunrong Road, Kunming, Yunnan 650500, China.

出版信息

Burns. 2022 May;48(3):639-648. doi: 10.1016/j.burns.2021.06.004. Epub 2021 Jun 21.

Abstract

Pomegranate peel extract (PPE), a polyphenolic compound derived from pomegranate, has been widely concerned for its anti-oxidant, anti-inflammatory, and bacteriostatic effects. The potential therapeutic effect of PPE on burn injury was investigated, and its possible mechanisms were explored. Minipigs with second-degree burn were treated with PPE, Jing Wan Hong, and silver sulfadiazine. Hematoxylin-eosin (HE) staining was performed to detect burn severity, and then biological tissues were biopsied on days 0, 7, 14, 21, and 28 after administration. Immunohistochemistry, western blot, and real-time polymerase chain reaction (RT-PCR) were used to detect the protein and mRNA expression levels of VEGF-A and TGF-β1 in skin tissues after treatment with PPE. Furthermore, the skin wound healing at different time points was monitored by macroscopic observation. HE showed that after 28-day PPE treatment, the morphology of the skin tissue showed a significant improvement. Macroscopic data monitoring indicated that the decrustation and fur growing time was shortened. Meanwhile, the rate of wound healing increased after PPE treatment. The combination of immunohistochemistry, western blotting, and RT-PCR showed that after PPE treatment, expression of VEGF-A and TGF-β1 increased sharply on day 7, maintaining a high level until day 14, showing a downward trend on day 21, and approaching normal levels on day 28. However, in the model group, the protein and mRNA expression levels of VEGF-A and TGF-β1 increased on day 28 after burn injury, which was a slow process. Results indicated that compared with the model group, the peak expression level of VEGF-A and TGF-β1 was earlier, which was consistent with decrustation, shortening of fur growing time, and improvement of wound healing rate in minipig second-degree burn model. PPE showed a significant promoting effect on minipig second-degree burn model, which might be associated with the upregulation of the protein and gene expression levels of VEGF-A and TGF-β1.

摘要

石榴皮提取物(PPE)是一种源自石榴的多酚类化合物,因其抗氧化、抗炎和抑菌作用而受到广泛关注。本研究探讨了PPE对烧伤的潜在治疗作用,并探究了其可能的作用机制。将二度烧伤的小型猪分别用PPE、京万红和磺胺嘧啶银进行治疗。采用苏木精-伊红(HE)染色检测烧伤严重程度,并在给药后第0、7、14、21和28天对生物组织进行活检。运用免疫组织化学、蛋白质印迹法和实时聚合酶链反应(RT-PCR)检测PPE处理后皮肤组织中血管内皮生长因子A(VEGF-A)和转化生长因子β1(TGF-β1)的蛋白质和mRNA表达水平。此外,通过宏观观察监测不同时间点的皮肤伤口愈合情况。HE染色显示,PPE治疗28天后,皮肤组织形态有显著改善。宏观数据监测表明,脱痂和毛发生长时间缩短。同时,PPE治疗后伤口愈合速度加快。免疫组织化学、蛋白质印迹法和RT-PCR联合检测显示,PPE治疗后,VEGF-A和TGF-β1的表达在第7天急剧增加,至第14天保持高水平,第21天呈下降趋势,第28天接近正常水平。然而,模型组中,烧伤后第28天VEGF-A和TGF-β1的蛋白质和mRNA表达水平才升高,这是一个缓慢的过程。结果表明,与模型组相比,VEGF-A和TGF-β1的峰值表达水平出现得更早,这与小型猪二度烧伤模型中的脱痂、毛发生长时间缩短以及伤口愈合速度加快相一致。PPE对小型猪二度烧伤模型具有显著的促进作用,这可能与VEGF-A和TGF-β1的蛋白质和基因表达水平上调有关。

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