Kaya Cemre S, Yılmaz Evrim O, Akdeniz-Doğan Zeynep D, Yucesoy Can A
Institute of Biomedical Engineering, Boğaziçi University, Istanbul, Turkey.
Department of Plastic Reconstructive and Aesthetic Surgery, Marmara University, Istanbul, Turkey.
Front Bioeng Biotechnol. 2020 Jun 30;8:738. doi: 10.3389/fbioe.2020.00738. eCollection 2020.
Botulinum toxin type-A (BTX-A) is widely used for spasticity management and mechanically aims at reducing passive resistance at the joint and widening joint range of movement. However, recent experiments on acute BTX-A effects showed that the injected rat tibialis anterior (TA) muscle's passive forces increased, and the length range of active force exertion ( ) did not change. Additionally, BTX-A was shown to spread into non-injected muscles in the compartment and affect their mechanics. Whether those effects persist in the long term is highly important, but unknown. The aim was to test the following hypotheses with experiments conducted in the anterior crural compartment of the rat: In the long term, BTX-A (1) maintains , (2) increases passive forces of the injected TA muscle, and (3) spreads into non-injected extensor digitorum longus (EDL) and the extensor hallucis longus (EHL) muscles, also affecting their active and passive forces. Male Wistar rats were divided into two groups: BTX-A and Control (0.1 units of BTX-A or only saline was injected into the TA). Isometric forces of the muscles were measured simultaneously 1-month post-injection. The targeted TA was lengthened, whereas the non-targeted EDL and EHL were kept at constant length. Hydroxyproline analysis was done to quantify changes in the collagen content of studied muscles. Two-way ANOVA test (for muscle forces, factors: TA length and animal group) and unpaired or Mann-Whitney test (for and collagen content, where appropriate) were used for statistical analyses ( < 0.05). BTX-A caused significant effects. TA: active forces decreased (maximally by 75.2% at short and minimally by 48.3%, at long muscle lengths), decreased (by 22.9%), passive forces increased (by 12.3%), and collagen content increased (approximately threefold). EDL and EHL: active forces decreased (up to 66.8%), passive force increased (minimally by 62.5%), and collagen content increased (approximately twofold). Therefore, hypothesis 1 was rejected and 2 and 3 were confirmed indicating that previously reported acute BTX-A effects persist and advance in the long term. A narrower and an elevated passive resistance of the targeted muscle are unintended mechanical effects, whereas spread of BTX-A into other compartmental muscles indicates the presence of uncontrolled mechanical effects.
A型肉毒杆菌毒素（BTX-A）被广泛用于治疗痉挛，其作用机制旨在降低关节处的被动阻力并扩大关节活动范围。然而，最近关于BTX-A急性效应的实验表明，注射BTX-A后大鼠胫前肌（TA）的被动力增加，而主动力施加的长度范围（ ）并未改变。此外，研究表明BTX-A会扩散到注射部位所在肌间隔内的未注射肌肉中，并影响其力学性能。这些效应是否长期持续存在至关重要，但目前尚不清楚。本研究旨在通过在大鼠小腿前肌间隔进行的实验来验证以下假设：从长期来看，BTX-A（1）维持 ，（2）增加注射的TA肌肉的被动力，（3）扩散到未注射的趾长伸肌（EDL）和拇长伸肌（EHL）中，并影响它们的主动力和被动力。将雄性Wistar大鼠分为两组：BTX-A组和对照组（分别向TA注射0.1单位的BTX-A或仅注射生理盐水）。在注射后1个月同时测量肌肉的等长力。对目标TA进行拉伸，而未靶向的EDL和EHL保持恒定长度。进行羟脯氨酸分析以量化所研究肌肉中胶原蛋白含量的变化。采用双向方差分析（用于肌肉力量，因素：TA长度和动物组）和不成对 检验或Mann-Whitney 检验（适用于 和胶原蛋白含量）进行统计分析（ < 0.05）。BTX-A产生了显著影响。TA：主动力降低（在短肌肉长度时最大降低75.2%，在长肌肉长度时最小降低48.3%）， 降低（降低22.9%），被动力增加（增加12.3%），胶原蛋白含量增加（约为三倍）。EDL和EHL：主动力降低（高达66.8%），被动力增加（最小增加62.5%），胶原蛋白含量增加（约为两倍）。因此，假设1被否定，假设2和3得到证实，这表明先前报道的BTX-A急性效应在长期内持续存在并进一步发展。目标肌肉较窄的 和升高的被动阻力是意外的力学效应，而BTX-A扩散到其他肌间隔肌肉表明存在未受控制的力学效应。
