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Choline administration attenuates aspects of the dystrophic pathology in mdx mice

机译:胆碱给药减轻了 mdx 小鼠营养不良性病理的某些方面

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Background & aimsDystrophic muscle fibres are fragile and prone to breakage, leading to impaired Ca2+homeostasis and excessive inflammation, resulting in muscle wasting and weakness. Choline, an essential water-soluble nutrient, is involved in multiple biological processes, including modulation of inflammation and oxidative stress. We tested the hypothesis that choline supplementation would ameliorate the dystrophic pathology inmdxmice.MethodsThree-week old malemdxmice (n?=?40) were fed control purified laboratory chow (CON; n?=?20) or a choline-enriched diet (5?g/kg choline; CHL, n?=?20) for four weeks. Rotarod performance, grip strength and running (wheel) distance were assessed during treatment. Markers of Ca2+-handling, inflammation, oxidative stress and fibrosis were measured in the diaphragm, quadriceps muscle and the liver.ResultsCholine-treatedmdxmice displayed less macrophage (CD68 -33%, P?
机译:背景与目的营养不良性肌纤维易碎且容易断裂,从而导致Ca2 +稳态失衡和过度炎症,导致肌肉消瘦和虚弱。胆碱是一种必需的水溶性营养素,它参与多种生物过程,包括调节炎症和氧化应激。我们检验了补充胆碱可改善营养不良性疾病的假说的方法。方法给三周大的雄性mdxmice(n?=?40)喂饲对照纯净实验室食物(CON; n?=?20)或富含胆碱的饮食(5? g / kg胆碱; CHL,n?=?20)持续4周。在治疗过程中评估了旋转架性能,抓地力和行驶(车轮)距离。在横diaphragm膜,股四头肌和肝脏中测量Ca2 +处理,炎症,氧化应激和纤维化的标志物。结果经胆碱处理的mdx小鼠显示出较少的巨噬细胞(CD68 -33%,P <0.05)和胶原蛋白浸润(34%,与未经处理的mdx小鼠相比,隔膜中的Tgfβ3mRNA表达降低(P 0.05),Tgfβ3mRNA表达降低(P 0.05)。与未治疗的mdxmice相比,补充胆碱可增加最大SERCA活性(38%,P 0.05)并减少炎症标记(Tnfα,F4 / 80和Cd206mRNA,P 0.05)。胆碱治疗后肝脏的Acta2mRNA减少(P 0.05),血清ALT水平升高(P 0.01)。两组的全身功能分析无差异。结论补充胆碱可减轻营养不良性病理的进展。尽管胆碱不会改变功能,但减少纤维化与增加DMD疗法的疗效在临床上相关。

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