Longino D, Frank Cy, Leonard T R, Vaz Marco A, Herzog Walter
Faculty of Medicine, University of Calgary, Calgary, AB, Canada T2N 1N4.
J Orthop Res. 2005 Nov;23(6):1411-8. doi: 10.1016/j.orthres.2005.02.016.1100230625. Epub 2005 Jun 1.
Osteoarthritic patients show only a weak association between radiographic signs of joint disease and joint pain and disability. Conversely, muscle weakness is one of the earliest and most common symptoms of patients with osteoarthritis (OA). However, while many experimental models of osteoarthritis include a component of muscular weakness, no model has isolated this factor satisfactorily. Therefore, the purpose of this study was to develop and validate an experimental animal model of muscle weakness for future use in the study of OA. Botulinum Type-A toxin (BTX-A) was uni-laterally injected into the quadriceps musculature of New Zealand white rabbits (3.5 units/kg). Isometric knee extensor torque at a range of knee angles and stimulation frequencies, and quadriceps muscle mass, were quantified for control animals, and at one- and six-months post-repeated injections, in both, the experimental and the contralateral hindlimb. Ground reaction forces were measured in all animals while hopping across two force platforms. Isometric knee extension torque and quadriceps muscle mass was systematically decreased in the experimental hindlimb. Vertical ground reaction forces in the push off phase of hopping were also decreased in the experimental compared to control hindlimbs. We conclude that BTX-A injection into the rabbit musculature creates functional and absolute muscle weakness in a reproducible manner. Therefore, this model may be used to systematically study the possible effects of muscle weakness on joint degeneration, either as an isolated intervention, or in combination with other interventions (anterior cruciate ligament transection, meniscectomy) known to create knee joint degeneration.
骨关节炎患者关节疾病的影像学表现与关节疼痛及功能障碍之间的关联较弱。相反，肌肉无力是骨关节炎（OA）患者最早出现且最常见的症状之一。然而，尽管许多骨关节炎实验模型都包含肌肉无力这一因素，但尚无模型能令人满意地分离出该因素。因此，本研究的目的是开发并验证一种肌肉无力的实验动物模型，以供未来用于OA研究。将A型肉毒杆菌毒素（BTX-A）单侧注射到新西兰白兔的股四头肌中（3.5单位/千克）。对对照动物以及在重复注射后1个月和6个月时，分别在实验侧和对侧后肢，定量测量一系列膝关节角度和刺激频率下的等长伸膝扭矩以及股四头肌质量。在所有动物跨越两个测力平台跳跃时测量地面反作用力。实验侧后肢的等长伸膝扭矩和股四头肌质量系统性降低。与对照后肢相比，实验侧后肢在跳跃蹬离阶段的垂直地面反作用力也降低。我们得出结论，向兔肌肉组织注射BTX-A可重复性地造成功能性和绝对性肌肉无力。因此，该模型可用于系统研究肌肉无力对关节退变的可能影响，既可以作为单独干预措施，也可以与已知会导致膝关节退变的其他干预措施（前交叉韧带切断术、半月板切除术）联合使用。
