Characteristic changes in morphology and function of skeletal muscles in a rat model of “tendon off-position”
Yang Zongrui1, 2, Ge Haiya1, 2, Shi Jinyu1, 2, Wang Zhengming1, 2, Wang Yuanyuan1, 2, Li Zhengyan1, 2, Du Guoqing1, 2, Zhan Hongsheng1, 2
1Shi’s Center of Orthopedics and Traumatology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; 2Institute of Traumatology & Orthopedics, Shanghai Academy of Traditional Chinese Medicine, Shanghai 201203, China
Abstract: BACKGROUND: “Tendon off-position” is a disease name included in the International Classification of Diseases 11th Revision, and also a clinical indication of manipulation, acupuncture and other treatments. However, its specific mechanism is still unclear. It is urgent to establish an animal model that can reflect the clinical and pathological characteristics of “tendon off-position,” so as to further study the mechanism of effective clinical treatments.
OBJECTIVE: To establish an animal model of “tendon off-position” in rats based on isometric contraction of skeletal muscles, and to explore the changes of skeletal muscle function and morphological phenotype after “tendon off-position.”
METHODS: Sixty rats were randomly divided into control group, static-loading group and extra loading group, with twenty rats in each group. Rats in the control group were kept normally without treatment. In the latter two groups, the rats were fixed by the self-made static-loading modeling device and a static-loading (the body mass of each rats was applied as the static-loading) was applied to cause sustained isometric contraction of the upper limb muscles. Then, animal models of “tendon off-position” were successfully established. In the extra loading group, 50% of the body mass was added to the ankle joint after modeling. The skeletal muscle samples were harvested at 2 and 4 weeks after modeling. The changes of limb grip strength, wet mass of skeletal muscle, and serum levels of creatine kinase-muscle and lactate dehydrogenase A were measured, and the changes of skeletal muscle histomorphology and ultrastructure were observed.
RESULTS AND CONCLUSION: At 2 weeks after modeling, the rats in the static-loading group and extra loading group showed significantly decreased grip strength and wet muscle mass, significantly increased serum levels of creatine kinase-muscle and lactate dehydrogenase A, and abnormal muscle fiber morphology and structure accompanied by a large number of deposited collagen fibers. Electron microscopy results showed that the structure of myofibrils was disordered, the Z-line was distorted, and the light and dark boundaries were blurred. At 4 weeks after modeling, the grip strength of the model rats was increased compared with that at 2 weeks, the serum creatine kinase-muscle and lactate dehydrogenase A levels were decreased, and the changes of muscle fiber morphology and ultrastructure were recovered to varying degrees. It is suggested that the rat skeletal muscle injury model based on continuous isometric contraction of skeletal muscle can well reflect the pathological characteristics of “tendon off-position” at 2 weeks, and can be used to study the mechanism of acupuncture and manipulation in the treatment of “tendon off-position.”
Key words: “tendon off-position”, TCM syndrome, skeletal muscle, isometric contraction, creatine kinase, lactate dehydrogenase, animal model