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Histological features of masticatory muscles after botulinum toxin A injection into the right masseter muscle of dystrophin deficient (mdx-) mice.
Annals of Anatomy ( IF 2.0 ) Pub Date : 2020-01-21 , DOI: 10.1016/j.aanat.2020.151464
Ute Ulrike Botzenhart 1 , Tomasz Gredes 1 , Ricarda Gerlach 1 , Ines Zeidler-Rentzsch 1 , Tomasz Gedrange 1 , Christiane Keil 1
Affiliation  

OBJECTIVE/BACKGROUND The most frequently used animal model for human DMD (Duchenne muscular dystrophy) research is the mdx mouse. In both species, characteristic histological changes like inflammation, muscle fiber degeneration and fibrosis are the same, but in contrast to humans, in mdx mice, phases of muscle fiber degeneration are compensated by regeneration processes. AIM Therefore, the interest of this study was to evaluate histological features in masticatory muscles after BTX-A injection into the right masseter muscle of wild type and dystrophic (mdx) mice, illustrating de- and regeneration processes induced by this substance. MATERIAL AND METHODS The right masseter muscle of 100 days old healthy and mdx mice were selectively paralyzed by a single intramuscular BTX-A injection. Masseter as well as temporal muscle of injection and non-injection side were carefully dissected 21 days and 42 days after injection, respectively, and fiber diameter, cell nuclei position, necrosis and collagen content were analyzed histomorphologically in order to evaluate de- and regeneration processes in these muscles. Statistical analysis was performed using SigmaStat Software and Mann Whitney U-test (significance level: p < 0.05). RESULTS At both investigation periods and in both mouse strains fiber diameter was significantly reduced and collagen content was significantly increased in the right injected masseter muscle whereas fiber diameters in mdx mice were much smaller, and these differences were even more apparent at the second investigation period. Necrosis and central located nuclei could generally be found in all mdx mice muscles investigated with an amount of centronucleation exceeding 60%, and a significant increase of necrosis six weeks after injection. In wild type mice central located nuclei could primarily be found in the treated masseter muscle with a portion of 2.7%, and this portion decreased after six weeks, whereas in mdx mice a decrease could also be seen in the non-injected muscles. In contrast, in wild type mice necrosis was not apparent at any time and in all muscles investigated. CONCLUSION From our results it can be concluded that in mdx mice masticatory muscles de- and regeneration processes were extended, triggered by a selective BTX-A injection, or mdx mice at this age, independently of BTX-A treatment, went through another cycle of de- and regeneration as a characteristic of this disease.

中文翻译:

肉毒杆菌毒素A注入肌营养不良蛋白缺乏症(mdx-)小鼠的右咬肌后的咀嚼肌的组织学特征。

目的/背景用于人类DMD(杜氏肌营养不良症)研究的最常用动物模型是mdx小鼠。在这两个物种中,炎症,肌肉纤维变性和纤维化等特征性组织学变化是相同的,但是与人类相反,在mdx小鼠中,肌肉纤维变性的阶段被再生过程所补偿。目的因此,这项研究的目的是评估在野生型和营养不良(mdx)小鼠的右咬肌中注射BTX-A后咀嚼肌的组织学特征,以说明该物质引起的脱细胞和再生过程。材料和方法通过单次肌肉内BTX-A注射选择性使100天大的健康和mdx小鼠的右咬肌肌肉麻痹。分别在注射后21天和42天仔细解剖注射和非注射侧的咬肌以及颞肌,并组织形态分析纤维直径,细胞核位置,坏死和胶原含量,以评估脱细胞和再生过程在这些肌肉中。使用SigmaStat软件和Mann Whitney U检验进行统计学分析(显着性水平:p <0.05)。结果在两个研究阶段和两个小鼠品系中,右侧注射的咬肌中的纤维直径均显着减少,胶原蛋白含量显着增加,而mdx小鼠中的纤维直径要小得多,并且这些差异在第二个研究期更为明显。通常在所调查的所有mdx小鼠肌肉中都发现坏死和位于中央的细胞核,其核核转移量超过60%,注射后六周坏死显着增加。在野生型小鼠中,位于中央的中枢核主要存在于经治疗的咬肌中,其比例为2.7%,该比例在六周后下降,而在mdx小鼠中,未注射的肌肉中也可见到下降。相反,在野生型小鼠中,在任何时候和所研究的所有肌肉中,坏死都不明显。结论根据我们的结果,可以得出结论,在mdx小鼠中,咀嚼肌的去变性和再生过程是由选择性BTX-A注射触发的,或者在这个年龄段的mdx小鼠,独立于BTX-A治疗而延长,
更新日期:2020-01-21
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