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评估肩峰下撞击在肩袖肌腱病中的作用:一种新型大鼠模型的建立与分析。

Evaluating the role of subacromial impingement in rotator cuff tendinopathy: development and analysis of a novel rat model.

机构信息

Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY, USA; Institute of Sports Medicine, Peking University Third Hospital, Beijing, China.

Orthopedic Soft Tissue Research Program, Hospital for Special Surgery, New York, NY, USA.

出版信息

J Shoulder Elbow Surg. 2022 Sep;31(9):1898-1908. doi: 10.1016/j.jse.2022.02.041. Epub 2022 Apr 14.

Abstract

BACKGROUND

Subacromial impingement of the rotator cuff caused by variations in acromial anatomy or altered glenohumeral kinematics leads to inflammation and degeneration of the rotator cuff, ultimately contributing to the development of tendinopathy. However, the underlying cellular and molecular changes in the impinged tendon remain poorly understood. Because the rat is an accepted model for rotator cuff studies, we have developed a rat model to study rotator cuff tendinopathy.

METHODS

Forty-four adult male Sprague-Dawley rats were allocated to one of 4 study groups: intact control group (group 1, n = 11); bilateral subacromial surgical clip placement to induce supraspinatus impingement for 2 weeks (group 2, n = 11), 4 weeks (group 3, n = 11), and 8 weeks (group 4, n = 11). Bilateral shoulder specimens were harvested for biomechanical testing, histology, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis.

RESULTS

Radiography confirmed that all microvascular clips remained in stable position in the subacromial space. Gross inspection of supraspinatus tendon specimens in the impingement groups revealed changes in tendon morphology at the enthesis and midsubstance. Biomechanical evaluation demonstrated decreased supraspinatus tendon failure force and tissue stiffness at all time points compared with control tendons. Semiquantitative scoring of histologic specimens demonstrated significant, persistent tendinopathic changes over 8 weeks. qRT-PCR analysis of impinged tendon specimens demonstrated upregulation of gene expression for Col3 and Mmp14 in the impingement groups compared with control groups. In muscle samples, significant upregulation was seen in the expression of genes that are commonly associated with muscle atrophy (MuRF1 and Ube2b) and fatty infiltration (Fabp4, Pparg2, and Klf15).

CONCLUSION

This new rat subacromial impingement model creates cellular and molecular changes consistent with the development of rotator cuff tendinopathy. The results of this study may serve as a baseline for future investigation.

摘要

背景

肩袖的盂肱关节上缘撞击是由肩峰解剖结构的变化或盂肱关节运动学的改变引起的,导致肩袖的炎症和变性,最终导致肌腱病的发展。然而,撞击肌腱内的细胞和分子变化仍知之甚少。由于大鼠是研究肩袖的公认模型,我们已经开发了一种大鼠模型来研究肩袖肌腱病。

方法

44 只成年雄性 Sprague-Dawley 大鼠被分配到以下 4 个研究组之一:完整对照组(第 1 组,n=11);双侧肩峰下手术夹放置以诱导冈上肌撞击 2 周(第 2 组,n=11)、4 周(第 3 组,n=11)和 8 周(第 4 组,n=11)。采集双侧肩袖标本进行生物力学测试、组织学和实时定量聚合酶链反应(qRT-PCR)分析。

结果

放射照相术证实所有微血管夹均稳定地位于肩峰下间隙内。撞击组冈上肌腱标本的大体检查显示在附著点和肌腱中部出现了肌腱形态的变化。生物力学评估显示,与对照组肌腱相比,所有时间点的冈上肌腱断裂力和组织刚度均降低。组织学标本的半定量评分显示,在 8 周内肌腱病的变化持续存在。qRT-PCR 分析显示,与对照组相比,撞击组的 Col3 和 Mmp14 基因表达上调。在肌肉样本中,与肌肉萎缩(MuRF1 和 Ube2b)和脂肪浸润(Fabp4、Pparg2 和 Klf15)相关的基因表达显著上调。

结论

这种新的大鼠肩峰下撞击模型产生了与肩袖肌腱病发展一致的细胞和分子变化。本研究的结果可以作为未来研究的基线。

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