用桔梗进行短期治疗会加重 mdx 小鼠的损伤表型

David Feder, T. Hermes, Lucas Prezotto Giordani, B. Bertassoli, Giuliana Petri, Fabio Perazzo, F. Fonseca, Alzira A S Carvalho
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摘要

简介:Uncaria tomentosa (Willd. ex Roem. & Schult.) DC.(茜草科)或 UT 是一种药用植物,具有抗病毒、抗突变、抗炎和抗氧化特性。杜氏肌营养不良症(DMD)是一种严重的肌肉萎缩性疾病,由肌营养不良蛋白基因突变引起,这种缺陷会导致肌浆蛋白不稳定、炎症、肌肉变性和纤维化。研究目的考虑到炎症对肌营养不良症进展的重要性以及UT的抗炎活性,我们在本研究中评估了口服UT提取物是否能改善DMD模型mdx小鼠的肌营养不良症。研究方法八周大的雄性 mdx 小鼠每天口服 200 毫克/千克体重的UT,持续 6 周。对一般组织病理学进行分析,并评估肌肉肿瘤坏死因子α、转化生长因子-β、肌生成素和骨生成素的转录水平。测量了小鼠维持肢体张力以对抗重力的能力。数据用非配对的学生 t 检验进行分析。结果从形态上看,未经处理和经UT处理的动物都表现出细胞核内化、内膜结缔组织增加和肌纤维直径变化。UT治疗动物的体重和肌力明显下降。与未经处理的动物相比,经UT处理的动物血液中肌酸激酶含量更高。在胫骨前肌中,肌生长蛋白转录本在UT处理的动物中表达较高,而在膈肌中,转化生长因子-β转录本在UT处理的动物中表达较低。结论尽管之前的研究发现了UT的抗炎、抗增殖和抗癌作用,但该提取物表明,在对mdx小鼠进行短期治疗后,肌肉萎缩表型会恶化。
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Short-term treatment with Uncaria tomentosa aggravates the injury phenotype in mdx mice
Introduction: Uncaria tomentosa (Willd. ex Roem. & Schult.) DC. (Rubiaceae) or UT is a medicinal plant with antiviral, antimutagenic, anti-inflammatory and antioxidant properties. Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by mutations in the dystrophin gene; this deficiency leads to sarcolemma instability, inflammation, muscle degeneration and fibrosis. Objective: Considering the importance of inflammation to dystrophy progression and the anti-inflammatory activity of UT, in the present study we evaluated whether oral administration of UT extract would ameliorate dystrophy in the mdx mice, a DMD model. Methods: Eight-week-old male mdx mice were submitted to 200 mg/kg body weight daily UT oral administration for 6 weeks. General histopathology was analysed, and muscle tumor necrosis factor α, transforming growth factor-β, myostatin and osteopontin transcript levels were assessed. The ability of mice to sustain limb tension to oppose their gravitational force was measured. Data were analysed with the unpaired Student’s t-test. Results: Morphologically, both untreated and UT-treated animals exhibited internalised nuclei, increased endomysial connective tissue and variations in muscle fibre diameters. Body weight and muscle strength were significantly reduced in the UT-treated animals. Blood creatine kinase was higher in UT-treated compared to untreated animals. In tibialis anterior, myostatin, transcript was more highly expressed in the UT-treated while in the diaphragm muscle, transforming growth factor-β transcripts were less expressed in the UT-treated. Conclusion: While previous studies identified anti-inflammatory, antiproliferative and anticarcinogenic UT effects, the extract indicates worsening of dystrophic muscles phenotype after short-term treatment in mdx mice.
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