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前交叉韧带断裂后早期持续被动运动和跑步机治疗性运动产生软骨保护作用的临床前评估

A Preclinical Assessment of Early Continuous Passive Motion and Treadmill Therapeutic Exercises for Generating Chondroprotective Effects After Anterior Cruciate Ligament Rupture.

作者信息

Chang Nai-Jen, Lee Kuan-Wei, Chu Chih-Jou, Shie Ming-You, Chou Pei-Hsi, Lin Chih-Chan, Liang Peir-In

机构信息

Department of Sports Medicine, Kaohsiung Medical University, Kaohsiung City, Taiwan.

3D Printing Medical Research Center, China Medical University Hospital, North District, Taichung City, Taiwan.

出版信息

Am J Sports Med. 2017 Aug;45(10):2284-2293. doi: 10.1177/0363546517704847. Epub 2017 May 18.

DOI:10.1177/0363546517704847
PMID:28520463
Abstract

BACKGROUND

Anterior cruciate ligament (ACL) injury is a well-known risk factor for the development of posttraumatic osteoarthritis (PTOA). However, whether using continuous passive motion (CPM) with or without additional treadmill exercise (TRE) in early ACL injury might provide chondroprotective effects and further decrease the risk of PTOA has yet to be determined.

HYPOTHESIS

CPM may offer an enhanced chondroprotective effect, but TRE may attenuate that effect due to the mechanical stress on the joint and inflammatory cytokines in the joint.

STUDY DESIGN

Controlled laboratory study.

METHODS

Thirty adult New Zealand White male rabbits were randomly allocated to sedentary (SED), CPM, TRE, or CPM+TRE groups. Each rabbit underwent an ACL transection (ACLT) on the right knee, with the contralateral knee used as an internal control (sham). The 4 joint surfaces (ie, medial and lateral femoral condyles and tibial plateaus) were evaluated 4 weeks after surgery for gross appearance, histological characteristics, and quantitative osteoarthritis (OA) scores.

RESULTS

Overall, at the end of testing, the CPM group experienced the best protective therapeutic effects in all compartments. In gross appearance, CPM resulted in normal articular surfaces, while the TRE and SED groups exhibited surface abrasion. Histological analysis showed significant differences in articular cartilage status. The CPM group had significantly better histological OA scores ( P < .01), corresponding to the smoothest cartilage surface and sound chondrocyte and collagen arrangement. This group also showed abundant glycosaminoglycan (GAG) content and a sound growth microenvironment, with significantly lower expression levels of the inflammatory cytokine tumor necrosis factor α and the apoptotic marker caspase 3. In contrast, the TRE and SED groups showed several features of damage: distinct graded cartilage abrasion; damaged collagen fibers, corresponding to noticeable collagen type X (osteoarthritic cartilage); reduced cartilage thickness; fewer cartilaginous cells; and the appearance of chondrocyte clusters. These groups also showed loss of GAG, corresponding to higher levels of inflammatory cytokines and apoptosis of articular chondrocytes. Furthermore, the CPM+TRE group displayed visible pathological changes in the superficial cartilage, indicating that early loading exercise may contribute to osteoarthritis. The sham treatment showed no difference in the changes in all compartments between groups.

CONCLUSION

Immediate CPM therapy produces a superior in situ microenvironment for reducing the occurrence of PTOA after ACL injury without reconstruction in rabbits.

CLINICAL RELEVANCE

These data suggest that immediate application of CPM therapy may be necessary to create a sound microenvironment in joints and possibly to decrease the risk of PTOA without or while awaiting ACL reconstruction. In contrast, both early active loading exercise and inactivity lead to the development of PTOA.

摘要

背景

前交叉韧带(ACL)损伤是创伤后骨关节炎(PTOA)发生的一个众所周知的危险因素。然而,在ACL损伤早期使用持续被动运动(CPM)加或不加额外的跑步机运动(TRE)是否能提供软骨保护作用并进一步降低PTOA的风险,尚未确定。

假设

CPM可能提供增强的软骨保护作用,但TRE可能由于对关节的机械应力和关节内的炎性细胞因子而减弱这种作用。

研究设计

对照实验室研究。

方法

30只成年新西兰白兔雄性随机分为久坐不动(SED)、CPM、TRE或CPM + TRE组。每只兔子右膝进行ACL横断术(ACLT),对侧膝关节作为内部对照(假手术)。术后4周评估4个关节面(即内侧和外侧股骨髁以及胫骨平台)的大体外观、组织学特征和定量骨关节炎(OA)评分。

结果

总体而言,在测试结束时,CPM组在所有关节腔中均表现出最佳的保护性治疗效果。在大体外观上,CPM导致关节表面正常,而TRE组和SED组表现出表面磨损。组织学分析显示关节软骨状态存在显著差异。CPM组的组织学OA评分显著更好(P < .01),对应于最光滑的软骨表面以及良好的软骨细胞和胶原蛋白排列。该组还显示出丰富的糖胺聚糖(GAG)含量和良好的生长微环境,炎性细胞因子肿瘤坏死因子α和凋亡标志物半胱天冬酶3的表达水平显著降低。相比之下,TRE组和SED组表现出一些损伤特征:明显分级的软骨磨损;受损的胶原纤维,对应于明显的X型胶原(骨关节炎软骨);软骨厚度减少;软骨细胞数量减少;以及软骨细胞簇的出现。这些组还显示出GAG的丢失,对应于更高水平的炎性细胞因子和关节软骨细胞凋亡。此外,CPM + TRE组在表层软骨出现明显的病理变化,表明早期负重运动可能导致骨关节炎。假手术组在各关节腔的变化上组间无差异。

结论

立即进行CPM治疗可产生优越的原位微环境,以减少兔ACL损伤后未进行重建时PTOA的发生。

临床意义

这些数据表明,立即应用CPM治疗可能有必要在关节中创造良好的微环境,并可能降低在未进行或等待ACL重建时PTOA的风险。相比之下,早期主动负重运动和不活动都会导致PTOA的发生。

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