Department of Anatomy, ICB, Federal University of Alfenas (UNIFAL-MG), Alfenas, Minas Gerais, Brazil.
Department of Pharmacology, Centro Universitário FMABC (FMABC), Santo André, Sao Paulo, Brazil.
Int J Exp Pathol. 2024 Apr;105(2):75-85. doi: 10.1111/iep.12502. Epub 2024 Mar 13.
Duchenne muscular dystrophy (DMD) occurs due to genetic mutations that lead to a deficiency in dystrophin production and consequent progressive degeneration of skeletal muscle fibres, through oxidative stress and an exacerbated inflammatory process. The flavonoid trilobatin (TLB) demonstrates antioxidant and anti-inflammatory potential. Its high safety profile and effective action make it a potent therapy for the process of dystrophic muscle myonecrosis. Thus, we sought to investigate the action of TLB on damage in a DMD model, the mdx mouse. Eight-week-old male animals were treated with 160 mg/kg/day of trilobatin for 8 weeks. Control animals were treated with saline. Following treatment, muscle strength, serum creatine kinase (CK) levels, histopathology (necrotic myofibres, regenerated fibres/central nuclei, Feret's diameter and inflammatory area) and the levels of catalase and NF-κB (western blotting) of the quadriceps (QUA), diaphragm (DIA) and tibialis anterior (TA) muscles were measured. TLB was able to significantly increase muscle strength and reduce serum CK levels in dystrophic animals. The QUA of mdx mice showed a reduction in catalase and the number of fibres with a centralized nucleus after treatment with TLB. In the DIA of dystrophic animals, TLB reduced the necrotic myofibres, inflammatory area and NF-κB and increased the number of regenerated fibres and the total fibre diameter. In TA, TLB increased the number of regenerated fibres and reduced catalase levels in these animals. It is concluded that in the mdx experimental model, treatment with TLB was beneficial in the treatment of DMD.
杜氏肌营养不良症（DMD）是由于遗传突变导致肌营养不良蛋白产生不足，进而通过氧化应激和炎症过程加剧，导致骨骼肌纤维进行性退化。类黄酮三叶豆苷（TLB）具有抗氧化和抗炎作用。其安全性高且作用明显，是治疗肌营养不良性肌肉坏死的有效方法。因此，我们研究了 TLB 对 DMD 模型（mdx 小鼠）损伤的作用。8 周龄雄性动物每天用 160mg/kg 的三叶豆苷处理 8 周。对照组用生理盐水处理。治疗后，测量了股四头肌（QUA）、膈肌（DIA）和胫骨前肌（TA）的肌肉力量、血清肌酸激酶（CK）水平、组织病理学（坏死肌纤维、再生纤维/中央核、Feret 直径和炎症面积）以及 CAT 和 NF-κB（western blot）的水平。TLB 能够显著增加肌肉力量，降低 D 型动物的血清 CK 水平。与对照组相比，TLB 处理后的 mdx 小鼠的 QUA 中 CAT 水平和具有中央核的纤维数量降低。在 D 型动物的 DIA 中，TLB 减少了坏死肌纤维、炎症面积和 NF-κB，增加了再生纤维数量和总纤维直径。在 TA 中，TLB 增加了再生纤维的数量，降低了这些动物的 CAT 水平。综上所述，在 mdx 实验模型中，TLB 治疗对 DMD 有益。
