Hildebrand Kevin A, Zhang Mei, Germscheid Niccole M, Wang Chuan, Hart David A
McCaig Centre, Bone and Joint Institute, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Acta Orthop. 2008 Feb;79(1):116-25. doi: 10.1080/17453670710014860.
A recently developed animal model of posttraumatic contractures reflects the chronic stages of the human condition. To understand the initiation of the process, we evaluated the cellular, matrix, and growth factor changes in the joint capsule in the early stages of the animal model, which would not be possible in humans.
18 skeletally mature rabbits had intraarticular cortical windows removed from the medial and lateral femoral condyles, and the knee joint was immobilized. The contralateral unoperated limb served as a control. Equal numbers of rabbits were killed 2,4, and 6 weeks after surgery. Myofibroblast, mRNA, and protein determinations were done with immunohistochemistry, RT-PCR, and western blot, respectively.
Myofibroblast numbers were statistically significantly elevated in the joint capsules of the experimental knees as compared to control knees. The mRNA and protein levels for collagen types I and III, matrix metalloproteinases 1 and 13, and transforming growth factor beta1 were statistically significantly greater, and for tissue inhibitor of matrix metalloproteinases 1 significantly less, in the experimental capsules than in the control capsules.
The experimental joint capsule changes in the acute stages of posttraumatic contractures are similar to those in the chronic stages of the process in this model. Thus, it appears that the mechanisms that attenuate the acute stages of the response to injury are circumvented, contributing to a prolonged modulation of myofibroblast numbers, matrix molecules and growth factors, and leading to joint contractures. Thus, in clinical practice, new approaches to prevention of posttraumatic contractures should be implemented as soon as possible.
最近开发的创伤后挛缩动物模型反映了人类疾病的慢性阶段。为了解该过程的起始情况，我们评估了动物模型早期关节囊中细胞、基质和生长因子的变化，而这在人类中是无法做到的。
18只骨骼成熟的兔子，其股骨内外侧髁的关节内皮质窗口被移除，膝关节被固定。对侧未手术的肢体作为对照。术后2周、4周和6周分别处死等量的兔子。分别采用免疫组织化学、逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法进行肌成纤维细胞、信使核糖核酸（mRNA）和蛋白质的测定。
与对照膝关节相比，实验膝关节关节囊中的肌成纤维细胞数量在统计学上显著增加。与对照关节囊相比，实验关节囊中I型和III型胶原蛋白、基质金属蛋白酶1和13以及转化生长因子β1的mRNA和蛋白质水平在统计学上显著更高，而基质金属蛋白酶组织抑制剂1的水平显著更低。
在该模型中，创伤后挛缩急性期实验关节囊的变化与该过程慢性期的变化相似。因此，似乎损伤反应急性期的减弱机制被规避，导致肌成纤维细胞数量、基质分子和生长因子的调节延长，并导致关节挛缩。因此，在临床实践中，应尽快采用预防创伤后挛缩的新方法。
