Systematic review of pathologic markers in skin ischemia with and without reperfusion injury in microsurgical reconstruction: Biomarker alterations precede histological structure changes

IF 1.5 3区医学 Q3 SURGERY

Microsurgery Pub Date : 2024-02-15 DOI:10.1002/micr.31141

Ryan Khalaf BS, Daniela Duarte Bateman MD, Jose Reyes BS, Daniel Najafali BS, Antonio Rampazzo MD, PhD, Bahar Bassiri Gharb MD, PhD

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引用次数: 0

Abstract

Background

Ischemia and ischemia–reperfusion injury contribute to partial or complete flap necrosis. Traditionally, skin histology has been used to evaluate morphological and structural changes, however histology does not detect early changes. We hypothesize that morphological and structural skin changes in response to ischemia and IRI occur late, and modification of gene and protein expression are the earliest changes in ischemia and IRI.

Methods

A systematic review was performed in accordance with PRISMA guidelines. Studies reporting skin histology or gene/protein expression changes following ischemia with or without reperfusion injury published between 2002 and 2022 were included. The primary outcomes were descriptive and semi-quantitative histological structural changes, leukocyte infiltration, edema, vessel density; secondary outcomes were quantitative gene and protein expression intensity (PCR and western blot). Model type, experimental intervention, ischemia method and duration, reperfusion duration, biopsy location and time point were collected.

Results

One hundred and one articles were included. Hematoxylin and eosin (H&E) showed inflammatory infiltration in early responses (12–24 h), with structural modifications (3–14 days) and neovascularization (5–14 days) as delayed responses. Immunohistochemistry (IHC) identified angiogenesis (CD31, CD34), apoptosis (TUNEL, caspase-3, Bax/Bcl-2), and protein localization (NF-κB). Gene (PCR) and protein expression (western blot) detected inflammation and apoptosis; endoplasmic reticulum stress/oxidative stress and hypoxia; and neovascularization. The most common markers were TNF-α, IL-6 and IL-1β (inflammation), caspase-3 (apoptosis), VEGF (neovascularization), and HIF-1α (hypoxia).

Conclusion

There is no consensus or standard for reporting skin injury during ischemia and IRI. H&E histology is most frequently performed but is primarily descriptive and lacks sensitivity for early skin injury. Immunohistochemistry and gene/protein expression reveal immediate and quantitative cellular responses to skin ischemia and IRI. Future research is needed towards a universally-accepted skin injury scoring system.

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对显微外科重建中伴有或不伴有再灌注损伤的皮肤缺血病理标志物进行系统回顾：生物标志物的变化先于组织学结构的变化。

背景：缺血和缺血再灌注损伤会导致皮瓣部分或完全坏死。传统上，皮肤组织学被用来评估形态和结构变化，但组织学并不能检测到早期变化。我们假设，缺血和IRI引起的皮肤形态和结构变化发生较晚，而基因和蛋白质表达的改变是缺血和IRI最早发生的变化：方法：根据 PRISMA 指南进行了系统回顾。方法：根据 PRISMA 指南进行了系统综述，纳入了 2002 年至 2022 年间发表的报告缺血后皮肤组织学或基因/蛋白质表达变化的研究，无论是否存在再灌注损伤。主要结果为描述性和半定量组织学结构变化、白细胞浸润、水肿、血管密度；次要结果为定量基因和蛋白质表达强度（PCR 和 Western 印迹）。收集了模型类型、实验干预、缺血方法和持续时间、再灌注持续时间、活检位置和时间点：结果：共纳入 1001 篇文章。血栓素和伊红（H&E）显示炎症浸润为早期反应（12-24 小时），结构改变（3-14 天）和新生血管形成（5-14 天）为延迟反应。免疫组化（IHC）确定了血管生成（CD31、CD34）、凋亡（TUNEL、caspase-3、Bax/Bcl-2）和蛋白定位（NF-κB）。基因（PCR）和蛋白表达（western blot）检测炎症和细胞凋亡；内质网应激/氧化应激和缺氧；以及新生血管。最常见的标记物是 TNF-α、IL-6 和 IL-1β（炎症）、caspase-3（细胞凋亡）、VEGF（新生血管）和 HIF-1α（缺氧）：结论：对于缺血和内部损伤期间皮肤损伤的报告，目前尚无共识或标准。H&E组织学是最常用的方法，但主要是描述性的，对早期皮肤损伤缺乏敏感性。免疫组化和基因/蛋白表达揭示了皮肤缺血和IRI的即时和定量细胞反应。未来的研究需要建立一个普遍接受的皮肤损伤评分系统。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Microsurgery 医学-外科

CiteScore

3.80

自引率

19.00%

发文量

128

审稿时长

4-8 weeks

期刊介绍： Microsurgery is an international and interdisciplinary publication of original contributions concerning surgery under microscopic magnification. Microsurgery publishes clinical studies, research papers, invited articles, relevant reviews, and other scholarly works from all related fields including orthopaedic surgery, otolaryngology, pediatric surgery, plastic surgery, urology, and vascular surgery.