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聚脱氧核糖核苷酸和脱细胞胶原蛋白对大鼠跟腱损伤的治疗作用

Therapeutic Effects of Polydeoxyribonucleotide and Atelocollagen into Achilles Tendon Injury in a Rat Model.

作者信息

Kim Da-Sol, Hui Won Yu, Park Sung-Hee, Seo Jeong-Hwan, Ko Myoung-Hwan, Kim Gi-Wook

机构信息

Department of Physical Medicine and Rehabilitation, Jeonbuk National University Medical School, Jeonju, Republic of Korea.

Research Institute of Clinical Medicine - Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju, Republic of Korea.

出版信息

Orthop J Sports Med. 2025 Jun 2;13(6):23259671251324181. doi: 10.1177/23259671251324181. eCollection 2025 Jun.

Abstract

BACKGROUND

Treatment of Achilles tendon injury varied from surgical to nonsurgical management, such as immobilization, step-by-step physical therapy, or injection with regenerative agents. Regenerative treatment has been studied using polydeoxyribonucleotide (PDRN), atelocollagen, prolotherapy, platelet-rich plasma, and mesenchymal stem cells. PDRN and atelocollagen monotherapy have been known to promote mitigation of fibroblasts, synthesis of collagen fibers, and secretion of growth factors for tissue remodeling.

PURPOSE

To compare the therapeutic effects of PDRN, atelocollagen, and PDRN + atelocollagen treatments in rats with a partial Achilles tendon injury.

STUDY DESIGN

Controlled laboratory study.

METHODS

A total of 32 Sprague-Dawley rats, aged 8 weeks, were divided into 4 groups-normal saline, PDRN, atelocollagen, and PDRN + atelocollagen. The partial Achilles tendon injury was induced using punch biopsy tools. The treatment was administered 1 day after the injury. The biomechanical evaluation using load to failure and energy absorbed, histology related to inflammation and collagen fiber arrangement, and immunohistochemistry evaluation with collagen-I, transforming growth factor beta1, vascular endothelial growth factor (VEGF), and fibroblast growth factor were measured at 1 week and 4 weeks.

RESULTS

The tensile strength test conducted at week 4 after injury measured a significantly higher energy absorbed in the PDRN + atelocollagen group than that in the control group. The hematoxylin and eosin (H&E) stain showed that neutrophil invasion was significantly higher in the control group compared with the other groups. Collagen fiber arrangement relatively increased in the atelocollagen and PDRN + atelocollagen groups. After 4 weeks, H&E in all groups showed decreased neutrophil invasion and lower inflammation index. Immunohistochemistry exhibited increased levels of collagen I in the PDRN group compared with the control group and an increased level of VEGF in the PDRN + atelocollagen group compared with the other groups at week 1. After 4 weeks, a high expression of collagen I, transforming growth factor beta1, and fibroblast growth factor was observed in the PDRN and PDRN + atelocollagen groups; the expression of VEGF showed an upward trend in the atelocollagen group compared with the PDRN + atelocollagen group.

CONCLUSION

The combined use of PDRN and atelocollagen resulted in increased energy absorbed by the repaired tendons and increased expression of healing growth factors in a partial tendon injury rat model. These benefits appear to be greater than the use of either agent alone. The combined use of PDRN and atelocollagen should be investigated in human patients with tendon injuries.

CLINICAL RELEVANCE

PDRN and atelocollagen are commonly used in patients with tendon injuries; however, the comparison of therapeutic effects or synergistic effects has not yet been studied.

摘要

背景

跟腱损伤的治疗方法多样,包括手术治疗和非手术治疗,如固定、逐步进行物理治疗或注射再生剂。已使用聚脱氧核糖核苷酸(PDRN)、脱细胞胶原蛋白、增殖疗法、富血小板血浆和间充质干细胞进行再生治疗研究。已知PDRN和脱细胞胶原蛋白单一疗法可促进成纤维细胞的减轻、胶原纤维的合成以及组织重塑生长因子的分泌。

目的

比较PDRN、脱细胞胶原蛋白以及PDRN+脱细胞胶原蛋白治疗对部分跟腱损伤大鼠的治疗效果。

研究设计

对照实验室研究。

方法

将32只8周龄的Sprague-Dawley大鼠分为4组,即生理盐水组、PDRN组、脱细胞胶原蛋白组和PDRN+脱细胞胶原蛋白组。使用穿刺活检工具造成部分跟腱损伤。损伤后1天进行治疗。在第1周和第4周测量使用破坏载荷和吸收能量的生物力学评估、与炎症和胶原纤维排列相关的组织学以及用I型胶原、转化生长因子β1、血管内皮生长因子(VEGF)和成纤维细胞生长因子进行的免疫组织化学评估。

结果

损伤后第4周进行的拉伸强度测试显示,PDRN+脱细胞胶原蛋白组吸收的能量显著高于对照组。苏木精-伊红(H&E)染色显示,与其他组相比,对照组中性粒细胞浸润明显更高。脱细胞胶原蛋白组和PDRN+脱细胞胶原蛋白组胶原纤维排列相对增加。4周后,所有组的H&E显示中性粒细胞浸润减少,炎症指数降低。免疫组织化学显示,与对照组相比,PDRN组第1周时I型胶原水平升高,与其他组相比,PDRN+脱细胞胶原蛋白组第1周时VEGF水平升高。4周后,PDRN组和PDRN+脱细胞胶原蛋白组观察到I型胶原、转化生长因子β1和成纤维细胞生长因子的高表达;与PDRN+脱细胞胶原蛋白组相比,脱细胞胶原蛋白组VEGF表达呈上升趋势。

结论

在部分跟腱损伤大鼠模型中,PDRN和脱细胞胶原蛋白联合使用可使修复后的肌腱吸收的能量增加,愈合生长因子的表达增加。这些益处似乎大于单独使用任何一种药物。应在人类肌腱损伤患者中研究PDRN和脱细胞胶原蛋白的联合使用。

临床意义

PDRN和脱细胞胶原蛋白常用于肌腱损伤患者;然而,尚未研究其治疗效果或协同作用的比较。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4755/12130642/2087d2b4f3b9/10.1177_23259671251324181-fig1.jpg

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