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在胶原酶诱导的肌腱损伤中,肌腱中感觉神经肽的表达与愈合失败和与活动相关的肌腱疼痛有关。

Expression of sensory neuropeptides in tendon is associated with failed healing and activity-related tendon pain in collagenase-induced tendon injury.

机构信息

Department of Orthopaedics and Traumatology, The Chinese University of HongKong, Hong Kong SAR,

出版信息

Am J Sports Med. 2010 Apr;38(4):757-64. doi: 10.1177/0363546509355402. Epub 2010 Feb 5.

Abstract

BACKGROUND

Increase in expression of substance P (SP) and calcitonin gene-related peptide (CGRP) has been reported in clinical samples of tendinopathy.

PURPOSE

To examine the spatial-temporal expression of these neuropeptides as well as their association with activity-related tendon pain, matrix degeneration, failed healing, and pathologic calcification in an established collagenase-induced tendon injury rat model.

STUDY DESIGN

Controlled laboratory study.

METHODS

Collagenase or saline was injected into the patellar tendon of rats. At weeks 2, 4, 8, 12, and 16, just before the rats were sacrificed, the double-stance duration of rats was examined by gait analysis method. After sacrifice, the patellar tendons were harvested for histologic analysis and immunohistochemical staining of SP and CGRP.

RESULTS

There was an increase of SP and CGRP immunopositivity in tendon fibroblasts at week 2. The immunopositive signals decreased at weeks 4 and 8 and were observed in chondrocyte-like cells. At weeks 12 and 16, the immunopositive staining increased again and was observed in cells embedded in calcific deposits in addition to tendon fibroblasts and chondrocyte-like cells. The expression pattern was consistent with matrix degeneration, calcification, and failed healing in the animal model. There were significant positive correlations of immunopositivity of SP (rho = .502, P = .002) and CGRP (rho = .483, P = .003) with double-stance duration after collagenase injection.

CONCLUSION

There was increased expression of SP and CGRP after collagenase-induced tendon injury, and their expression was positively associated with double-stance duration. Clinical Relevance Substance P and CGRP might be involved in the pathogenesis and origin of pain of tendinopathy and could be the targets for future intervention.

摘要

背景

在肌腱病的临床样本中,已经报道了 P 物质(SP)和降钙素基因相关肽(CGRP)表达的增加。

目的

在已建立的胶原酶诱导的肌腱损伤大鼠模型中,研究这些神经肽的时空表达以及它们与与活动相关的肌腱疼痛、基质退化、愈合失败和病理性钙化的关系。

研究设计

对照实验室研究。

方法

向大鼠髌腱注射胶原酶或生理盐水。在 2、4、8、12 和 16 周,在大鼠被处死之前,通过步态分析方法检查大鼠的双足支撑时间。处死大鼠后,采集髌腱进行组织学分析和 SP 和 CGRP 的免疫组织化学染色。

结果

在第 2 周,肌腱成纤维细胞中 SP 和 CGRP 免疫阳性信号增加。第 4 和 8 周时,免疫阳性信号减少,并观察到软骨样细胞。在第 12 和 16 周时,免疫阳性染色再次增加,并观察到在钙化沉积物中嵌入的细胞,除了肌腱成纤维细胞和软骨样细胞。这种表达模式与动物模型中的基质退化、钙化和愈合失败一致。SP(rho =.502,P =.002)和 CGRP(rho =.483,P =.003)的免疫阳性与胶原酶注射后双足支撑时间之间存在显著的正相关。

结论

胶原酶诱导的肌腱损伤后 SP 和 CGRP 的表达增加,其表达与双足支撑时间呈正相关。

临床意义

P 物质和 CGRP 可能参与肌腱病的发病机制和疼痛的起源,可能成为未来干预的靶点。

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