杜氏肌营养不良症大鼠舌肌的巨舌症和较不先进的营养不良性改变。

Macroglossia and less advanced dystrophic change in the tongue muscle of the Duchenne muscular dystrophy rat.

机构信息

Laboratory of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.

Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.

出版信息

Skelet Muscle. 2022 Oct 19;12(1):24. doi: 10.1186/s13395-022-00307-7.

DOI:10.1186/s13395-022-00307-7

PMID:36258243

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9580129/

Abstract

BACKGROUND

Duchenne muscular dystrophy (DMD) is an X-linked muscle disease caused by a complete lack of dystrophin, which stabilizes the plasma membrane of myofibers. The orofacial function is affected in an advanced stage of DMD and this often leads to an eating disorder such as dysphagia. Dysphagia is caused by multiple etiologies including decreased mastication and swallowing. Therefore, preventing the functional declines of mastication and swallowing in DMD is important to improve the patient's quality of life. In the present study, using a rat model of DMD we generated previously, we performed analyses on the masseter and tongue muscles, both are required for proper eating function.

METHODS

Age-related changes of the masseter and tongue muscle of DMD rats were analyzed morphometrically, histologically, and immunohistochemically. Also, transcription of cellular senescent markers, and utrophin (Utrn), a functional analog of dystrophin, was examined.

RESULTS

The masseter muscle of DMD rats showed progressive dystrophic changes as observed in their hindlimb muscle, accompanied by increased transcription of p16 and p19. On the other hand, the tongue of DMD rats showed macroglossia due to hypertrophy of myofibers with less dystrophic changes. Proliferative activity was preserved in the satellite cells from the tongue muscle but was perturbed severely in those from the masseter muscle. While Utrn transcription was increased in the masseter muscle of DMD rats compared to WT rats, probably due to a compensatory mechanism, its level in the tongue muscle was comparable between WT and DMD rats and was similar to that in the masseter muscle of DMD rats.

CONCLUSIONS

Muscular dystrophy is less advanced in the tongue muscle compared to the masseter muscle in the DMD rat.

摘要

背景

杜氏肌营养不良症（DMD）是一种 X 连锁肌肉疾病，由肌营养不良蛋白的完全缺失引起，肌营养不良蛋白稳定肌纤维的质膜。口面功能在 DMD 的晚期受到影响，这通常导致吞咽困难等进食障碍。吞咽困难是由多种病因引起的，包括咀嚼和吞咽能力下降。因此，预防 DMD 中咀嚼和吞咽功能的下降对于提高患者的生活质量很重要。在本研究中，我们以前使用 DMD 大鼠模型进行了分析，对咀嚼肌和舌肌进行了分析，这两者都是正常进食功能所必需的。

方法

对 DMD 大鼠的咀嚼肌和舌肌进行形态学、组织学和免疫组织化学分析，研究年龄相关变化。还检查了细胞衰老标志物和肌营养不良蛋白（Utrn）的转录，Utrn 是肌营养不良蛋白的功能类似物。

结果

DMD 大鼠的咀嚼肌表现出与后肢肌肉相似的进行性营养不良变化，伴随着 p16 和 p19 的转录增加。另一方面，DMD 大鼠的舌由于肌纤维肥大而出现巨舌症，且营养不良变化较少。卫星细胞的增殖活性在舌肌中得以保留，但在咀嚼肌中则严重受损。虽然与 WT 大鼠相比，DMD 大鼠的咀嚼肌中 Utrn 的转录增加，可能是由于代偿机制，但 WT 大鼠和 DMD 大鼠的舌肌中 Utrn 的转录水平相当，与 DMD 大鼠的咀嚼肌中的转录水平相似。