框A HMGB1促进大鼠二度烧伤创面愈合

IF 3.2 3区医学 Q2 CRITICAL CARE MEDICINE

Burns Pub Date : 2025-03-13 DOI:10.1016/j.burns.2025.107456

Jiraroch Meevassana , Suvinai Jiraboonsri , Aurada Jitworawisut , Nicharee Khayanying , Paphawee Sirimaharaj , Supitcha Kamolratanakul , Nakarin Kitkumthorn , Apichai Angspatt , Apiwat Mutirangura

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引用次数: 0

摘要

dna损伤积累延迟烧伤创面愈合。我们之前的研究证实了HMGB1的Box A在DNA保护中的作用，产生了青年DNA缺口。过表达青年DNA缺口提高DNA耐久性和减少内源性DNA损伤。表达Box a的质粒转染是一种新的DNA编辑技术，可以防止DNA损伤。因此，我们假设Box A是一种促进烧伤创面愈合的治疗剂。方法采用包被磷酸钙纳米颗粒（Ca-P）的Box a质粒治疗大鼠烧伤创面。老鼠的背部有二级烧伤。本研究采用三组：对照组（生理盐水）、生理盐水 + Ca-P（对照组）和Box A质粒（n = 15只/组）。分别于创面诱导后0、7、14、21、28天拍摄创面，用Image J软件测量烧伤面积。分析烧伤皮肤组织切片的青年DNA缺口水平，进行组织学和免疫化学分析，然后根据DNA损伤标志物γH2AX和8-OhdG的表达水平进行评分。结果A盒质粒处理的伤口在伤后14 ~ 28天愈合明显改善（P <； 0.001）。与生理盐水和磷酸钙纳米颗粒处理组相比，Box A质粒处理组的总病理评分和DNA间隙在14 - 28天显著改善，并在第14天达到峰值（P <； 0.01）。第14 - 28天，与对照组相比，Box A组γ - h2ax和8-OhdG的表达也有所下降，其中第14和21天的表达水平差异最大。结论Box A质粒通过产生青年dna缺口，可能成为烧伤创面治疗的潜在靶点。

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Box A of HMGB1 improves second-degree burn wound healing in rats

Background

DNA damage accumulation delays burn wound healing. Our previous research demonstrated the function of Box A of HMGB1 in DNA protection, generating youth-DNA gaps. Overexpression of youth-DNA gaps enhances DNA durability and decreases endogenous DNA damage. Box A-expressing plasmid transfection is a new DNA-editing technology that prevents DNA damage. Thus, we hypothesized that Box A is a curative agent that improves burn wound healing.

Methods

In this study, we used a Box A plasmid coated with calcium phosphate nanoparticles (Ca-P) to treat burn wounds in rats. Second-degree burns were created on the backs of the rats. Three groups were used in this study: control (saline), saline + Ca-P (control), and Box A plasmid (n = 15 rats/group). The wounds were photographed 0, 7, 14, 21, and 28 days after wound induction and the burned areas were measured using Image J software. Burned skin tissue sections were analyzed for youth-DNA gap levels, subjected to histological and immunochemical analyses, and then scored according to the expression level of the DNA damage markers γH2AX and 8-OhdG.

Results

We observed improved wound healing in Box A plasmid-treated wounds from days 14 to 28 after injury (P < 0.001). A significant improvement in the total pathological score and DNA gaps in the Box A plasmid-treated group was observed at 14–28 days, with a peak on day 14 (P < 0.01) compared with that of the normal saline and calcium phosphate nanoparticle treated group. The expression of γH2AX and 8-OhdG was also decreased in the Box A group compared to controls on days 14–28, with the largest differences in expression levels observed on days 14 and 21.

Conclusions

Our results demonstrated that by producing youth-DNA gaps, Box A plasmid may be a potential therapeutic target in burn wound treatment.

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来源期刊

Burns 医学-皮肤病学

CiteScore

4.50

自引率

18.50%

发文量

304

审稿时长

72 days

期刊介绍： Burns aims to foster the exchange of information among all engaged in preventing and treating the effects of burns. The journal focuses on clinical, scientific and social aspects of these injuries and covers the prevention of the injury, the epidemiology of such injuries and all aspects of treatment including development of new techniques and technologies and verification of existing ones. Regular features include clinical and scientific papers, state of the art reviews and descriptions of burn-care in practice. Topics covered by Burns include: the effects of smoke on man and animals, their tissues and cells; the responses to and treatment of patients and animals with chemical injuries to the skin; the biological and clinical effects of cold injuries; surgical techniques which are, or may be relevant to the treatment of burned patients during the acute or reconstructive phase following injury; well controlled laboratory studies of the effectiveness of anti-microbial agents on infection and new materials on scarring and healing; inflammatory responses to injury, effectiveness of related agents and other compounds used to modify the physiological and cellular responses to the injury; experimental studies of burns and the outcome of burn wound healing; regenerative medicine concerning the skin.