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年轻和老年雌性小鼠皮肤伤口愈合延迟与生长因子释放差异有关,而非炎症细胞因子分泌。

Delayed cutaneous wound healing in young and old female mice is associated with differential growth factor release but not inflammatory cytokine secretion.

作者信息

Plum Melissa, Beier Justus P, Ruhl Tim

机构信息

Department of Plastic Surgery, Hand Surgery-Burn Center, University Hospital RWTH Aachen, Pauwelsstraße 30, 52074, Aachen, Germany.

出版信息

Biogerontology. 2025 Jan 8;26(1):37. doi: 10.1007/s10522-024-10179-7.

Abstract

The capacity for tissue repair during wound healing declines with age. A chronic low but systemic inflammatory status, often called "inflammaging", is considered a key factor that contributes to impaired tissue regeneration. This phenomenon has been substantiated by an increased number of immune cells in wound-tissue of old mice. Although immune cells coordinate an inflammatory response by their secretome the composition of the wound milieu has not been examined. In young (2 months) and old (18 months) female mice, excision wounds were induced using a punch biopsy device, i.e., the healing progress occurred through secondary intention. The closure rate was analyzed for 7 days. At days 1, 3 and 7 post-surgery, wound specimen were investigated for immunohistochemical detection of granulocytes, M1-macrophages and mesenchymal stem cells of the skin. The concentrations of inflammatory cytokines and regenerative growth factors were determined in tissue homogenates by ELISA. The carbonyl assay was used to determine protein oxidation. In old mice, the wound closure was delayed between days 1 and 3 post-surgery, as was the peak of immune cell infiltration. There was no age effect on the concentration of inflammatory cytokines, but wounds of young animals contained higher number of mesenchymal stem cells and increased levels of growth factors. Protein oxidation was increased with age. The present study suggests that a reduced regenerative capacity rather than an enhanced inflammatory score affected the tissue regeneration process in old mice.

摘要

伤口愈合过程中的组织修复能力会随着年龄的增长而下降。一种慢性的、程度较低但全身性的炎症状态,通常被称为“炎症衰老”,被认为是导致组织再生受损的关键因素。老年小鼠伤口组织中免疫细胞数量的增加证实了这一现象。尽管免疫细胞通过其分泌组协调炎症反应,但伤口微环境的组成尚未得到研究。在年轻(2个月)和老年(18个月)雌性小鼠中,使用打孔活检装置造成切除伤口,即愈合过程通过二期愈合发生。分析7天内的伤口闭合率。在术后第1、3和7天,对伤口标本进行免疫组织化学检测,以检测皮肤中的粒细胞、M1巨噬细胞和间充质干细胞。通过ELISA法测定组织匀浆中炎症细胞因子和再生生长因子的浓度。采用羰基测定法测定蛋白质氧化。在老年小鼠中,术后第1天至第3天伤口闭合延迟,免疫细胞浸润峰值也延迟。炎症细胞因子浓度没有年龄效应,但年轻动物的伤口含有更多的间充质干细胞和更高水平的生长因子。蛋白质氧化随着年龄的增长而增加。本研究表明,老年小鼠组织再生过程受再生能力降低而非炎症评分增加的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea2a/11711145/fdc0614cc787/10522_2024_10179_Fig1_HTML.jpg

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