大鼠局部肌肉萎缩实验模型的设计与建立

背景：目前研究肌肉与骨骼关系的常用动物模型均存在不足。已经有研究表明A型肉毒素可以使局部肌肉萎缩，而不影响周围其他的肌肉。目的：尝试是否可以用局部肌肉注射A型肉毒素的方法建立一种较为理想的肌肉萎缩的动物实验模型。方法：4月龄雄性Wistar大鼠25只，采用氯胺酮(0.2 mL/kg)和速眠新(0.2 mL/kg)肌注麻醉，在股骨背侧中部做一0.5 cm切口，暴露股四头肌，右侧股四头肌肌注2 U (0.2 mL)注射用A型肉毒毒素，左侧股四头肌注射等量生理盐水作为对照。分别于模型建立后的1，2，4，6和8周各取5只做肌肉大体、组织学观察。结果与结论：肌肉大体观察发现：与生理盐水侧对照组相比，注射A型肉毒素侧股四头肌体积明显缩小、质量明显降低(P < 0.01)；肌肉组织学观察发现：注射A型肉毒素侧股四头肌较生理盐水侧明显萎缩、肌纤维变细、肌纤维细胞核聚集、肌纤维与肌纤维之间间距变小。肉毒素侧1周和2周出现肌肉质量突降，4，6，8周之间肌肉质量增加缓慢，而各时间点生理盐水侧肌肉质量呈显著增加的趋势。通过对局部肌肉注射A型肉毒素可以理想地建立单个目的肌肉萎缩的实验模型，此模型操作性强、重复性好、特异性高，可应用于肌肉与骨骼关系的相关研究。

Design and establishment of a rat model of experimental local muscular atrophy

BACKGROUND: There were disadvantages of animal models in the study of the relationship of muscle and skeleton. Recent study has been demonstrated the effect of Botulinum toxin type A to atrophy local muscle without influencing the surrounding muscle. OBJECTIVE: To construct a reasonable animal model of local muscle atrophy by local injection of Botulinum toxin type A.METHODS: Totally 25 male Wistar rats of 4 months were subjected to ketamine (0.2 mL/kg) and Sumianxin (0.2 mL/kg) by intramuscular injection. A 0.5-cm incision was made on the middle of dorsal femur to expose quadriceps femoris. Right quadriceps femoris was injected with 2 Units (0.2 mL) of Botulinum toxin type A, and left quadriceps femoris of the same rat with the same amount of saline as controls. At 1, 2, 4, 6, 8 weeks after injection, 5 rats were used to take gross observation and histological examination.RESULTS AND CONCLUSION: Gross observation of the muscle tissue showed that, compared with self-controlled group, the volume and weight of the quadriceps femoris were decreased significantly (P < 0.01). The histological examination of muscle tissue showed the atrophy of the quadriceps femoris from experimental group was more obvious, the muscle fiber become thin, and the nuclei of the muscle fiber assemble together, with small distance between muscle fibers. Weight of the quadriceps femoris treated with Botulinum toxin type A was decreased at 1 and 2 weeks. The increase in weight of muscle was slow among muscle at 4, 6 and 8 weeks. The muscle weight showed an increased tendency in the saline side at various time points. Injecting Botulinum toxin type A into local muscle is a reasonable way to set up an experimental model of the atrophy of a destination muscle with strong practice, good repeatability, high stability, and may be used to examine the relationship of muscle and skeleton.