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基于 MAPK/ERK 通路探讨静态渐进牵伸联合体外冲击波疗法减轻大鼠膝关节挛缩的可能机制。

Possible mechanism of static progressive stretching combined with extracorporeal shock wave therapy in reducing knee joint contracture in rats based on MAPK/ERK pathway.

机构信息

Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, China; Research Center for Translational Medicine, The Second Hospital of Anhui Medical University, Hefei, China.

Department of Rehabilitation Medicine, The Second Hospital of Anhui Medical University, Hefei, China; Research Center for Translational Medicine, The Second Hospital of Anhui Medical University, Hefei, China; School of Basic Medical Sciences, Anhui Medical University, Hefei, China.

出版信息

Biomol Biomed. 2023 Mar 16;23(2):277-286. doi: 10.17305/bjbms.2022.8152.

DOI:10.17305/bjbms.2022.8152
PMID:36226595
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10113943/
Abstract

The study aimed to observe the therapeutic effect of static progressive stretching (SPS) combined with extracorporeal shock wave therapy (ESWT) on extension knee joint contracture in rats and the effect on the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway in the development of joint capsule fibrosis. Thirty-six Sprague Dawley rats were randomly divided into blank control group, immobilization model group, natural recovery group, ESWT intervention group, SPS intervention group, and SPS combined with ESWT intervention group. The left knee joints of the rats, except for the control group, were fixed with an external fixation brace for four weeks at full extension to form joint contractures. The therapeutic effect of each intervention was assessed by evaluating total and arthrogenic contracture, the number of total cells and collagen deposition in the anterior joint capsule, the protein levels of TGF-β1, FGF-2, and ERK2 in the anterior joint capsule, the mean optical density of upstream RAS and downstream ERK2 positive expression in the MAPK/ERK pathway. SPS in combination with ESWT was more effective in relieving joint contracture, improving the histopathological changes in the anterior joint capsule, and suppressing the high expression of target proteins and the overactivated MAPK/ERK pathway. The overactivated MAPK/ERK pathway was involved in the formation of extension knee joint contracture in rats. SPS in combination with ESWT was effective in relieving joint contracture and fibrosis of joint capsule. Moreover, the inhibition of the overactivated MAPK/ERK pathway may be the potential molecular mechanism for its therapeutic effect.

摘要

本研究旨在观察静态渐进性拉伸(SPS)联合体外冲击波疗法(ESWT)对大鼠伸展性膝关节挛缩的治疗效果,以及对关节囊纤维化发展过程中丝裂原活化蛋白激酶(MAPK)/细胞外信号调节激酶(ERK)通路的影响。36 只 Sprague Dawley 大鼠随机分为空白对照组、固定模型组、自然恢复组、ESWT 干预组、SPS 干预组和 SPS 联合 ESWT 干预组。除对照组外,其余大鼠左膝关节均采用外固定支具固定于完全伸展位 4 周,形成关节挛缩。通过评估总挛缩和关节源性挛缩、前关节囊总细胞数和胶原沉积、前关节囊 TGF-β1、FGF-2 和 ERK2 蛋白水平、MAPK/ERK 通路中上游 RAS 和下游 ERK2 阳性表达的平均光密度,评估各干预措施的治疗效果。SPS 联合 ESWT 更有效地缓解关节挛缩,改善前关节囊的组织病理学变化,抑制靶蛋白的高表达和过度激活的 MAPK/ERK 通路。过度激活的 MAPK/ERK 通路参与了大鼠伸展性膝关节挛缩的形成。SPS 联合 ESWT 可有效缓解关节挛缩和关节囊纤维化。此外,抑制过度激活的 MAPK/ERK 通路可能是其治疗效果的潜在分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e46f/10113943/8b9ea1b7e399/bjbms-2022-8152f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e46f/10113943/17b46410340d/bjbms-2022-8152f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e46f/10113943/8b9ea1b7e399/bjbms-2022-8152f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e46f/10113943/17b46410340d/bjbms-2022-8152f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e46f/10113943/07637734b107/bjbms-2022-8152f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e46f/10113943/d1976f1f218c/bjbms-2022-8152f3.jpg
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