Klein S M, Prantl L, Geis S, Felthaus O, Dolderer J, Anker A M, Zeitler K, Alt E, Vykoukal J
Center for Plastic-, Hand- and Reconstructive Surgery, University Hospital Regensburg, Germany.
Institute of Pathology, University of Regensburg, Regensburg, Germany.
Clin Hemorheol Microcirc. 2017;65(4):327-334. doi: 10.3233/CH-16195.
Duchenne muscular dystrophy (DMD) consists of a lack in the expression of the subsarcolemmal protein dystrophin causing progressive muscle dysfunction. Among the widely applied animal models in DMD research is the C57BL/1010ScSn-Dmdmdx mouse, commonly referred to as the "mdx mouse". The potential benefit of novel interventions in this model is often assessed by variables such as functional improvement, histological changes, and creatine kinase (CK) serum levels as an indicator for the extent of in situ muscle damage.
Our objective was to determine to what extent the serum CK-level serves a surrogate for muscle dysfunction.
In this trial mdx mice were subjected to a four-limb wire-hanging test (WHT) to assess the physical performance as a reference for muscle function. As CK is a component of the muscle fiber cytosol, its serum activity is supposed to positively correlate with progressing muscle damage. Hence serum CK levels were measured to detect the degree of muscle impairment. The functional tests and the serum CK levels were analyzed for their specific correlation.
Although physical performance decreased during the course of the experiment, latency to fall times in the WHT did not correlate with the CK level in mdx mice.
Our data suggests that the serum CK activity might be a critical parameter to monitor the progression of muscle impairment in mdx mice. Further this study emphasizes the complexity of the DMD phenotype in the mdx mouse, and the care with which isolated parameters in this model should be interpreted.
杜兴氏肌肉营养不良症（DMD）是由于肌膜下蛋白抗肌萎缩蛋白表达缺失导致进行性肌肉功能障碍。在DMD研究中广泛应用的动物模型是C57BL/1010ScSn-Dmdmdx小鼠，通常称为“mdx小鼠”。在该模型中，新干预措施的潜在益处通常通过功能改善、组织学变化和肌酸激酶（CK）血清水平等变量来评估，CK血清水平作为原位肌肉损伤程度的指标。
我们的目的是确定血清CK水平在多大程度上可作为肌肉功能障碍的替代指标。
在本试验中，对mdx小鼠进行四肢悬线试验（WHT）以评估身体性能，作为肌肉功能的参考。由于CK是肌纤维胞质溶胶的组成部分，其血清活性应与进行性肌肉损伤呈正相关。因此，测量血清CK水平以检测肌肉损伤程度。分析功能测试和血清CK水平之间的具体相关性。
尽管在实验过程中身体性能下降，但mdx小鼠在WHT中的跌落潜伏期与CK水平无关。
我们的数据表明，血清CK活性可能是监测mdx小鼠肌肉损伤进展的关键参数。此外，本研究强调了mdx小鼠中DMD表型的复杂性，以及在解释该模型中单个参数时应谨慎。
