Pasternak Björn, Fellenius Mårten, Aspenberg Per
Division of Orthopaedics, Department of Neuroscience and Locomotion, Faculty of Health Sciences, Linköping University, Sweden.
Acta Orthop Belg. 2006 Dec;72(6):756-60.
Doxycycline exhibits various effects apart from its antimicrobial activity, such as inhibition of matrix metalloproteinases (MMPs). MMPs, mainly collagenases and gelatinases, are capable of degrading virtually all constituents of the extracellular matrix and are critical to connective tissue remodelling and healing. We therefore hypothesised that doxycycline would negatively influence the rat tendon healing process and impede tendon regeneration. The Achilles tendon of 60 Sprague Dawley rats was transected transversely. The animals were treated with doxycycline, 130 mg/kg body weight/day. The healing tendons were evaluated mechanically at 5, 8 and 14 days. Doxycycline significantly decreased force at failure (p < 0.005) and energy uptake (p < 0.001). Doxycycline serum concentration was 3.4 (SD 1.0) microg/ml. In conclusion, tendon healing can be affected by doxycycline at clinically relevant serum concentrations. This observation might be of relevance to further studies exploring effects of MMP-inhibitors on tendon tissue.
除抗菌活性外,多西环素还具有多种作用,如抑制基质金属蛋白酶(MMPs)。MMPs主要包括胶原酶和明胶酶,几乎能够降解细胞外基质的所有成分,对结缔组织重塑和愈合至关重要。因此,我们推测多西环素会对大鼠肌腱愈合过程产生负面影响并阻碍肌腱再生。将60只Sprague Dawley大鼠的跟腱横向切断。给动物注射多西环素,剂量为130mg/kg体重/天。在第5、8和14天对愈合的肌腱进行力学评估。多西环素显著降低了断裂时的力(p<0.005)和能量吸收(p<0.001)。多西环素血清浓度为3.4(标准差1.0)μg/ml。总之,在临床相关血清浓度下,多西环素可影响肌腱愈合。这一观察结果可能与进一步探索MMP抑制剂对肌腱组织作用的研究有关。