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mdx 小鼠骨骼肌磷脂脂肪酸谱发生改变,并可预测疾病标志物。

Fatty acid profile of skeletal muscle phospholipid is altered in mdx mice and is predictive of disease markers.

机构信息

Department of Exercise Science and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08901, USA.

出版信息

Metabolism. 2012 Jun;61(6):801-11. doi: 10.1016/j.metabol.2011.10.019. Epub 2011 Dec 28.

Abstract

The mdx mouse is a model for Duchenne muscular dystrophy. The fatty acid (FA) composition in dystrophic muscle could potentially impact the disease severity. We tested FA profiles in skeletal muscle phospholipid (PL) and triglyceride in mdx and control (con) mice to assess associations with disease state as well as correlations with grip strength (which is lower in mdx) and serum creatine kinase (CK, which is elevated in mdx). Compared with con, mdx PL contained less docosahexaenoic acid (P < .001) and more linoleic acid (P = .001). Docosahexaenoic acid contents did not correlate with strength or serum CK. Linoleic acid content in PL was positively correlated with CK in mdx (P < .05) but not con. α-Linolenic acid content in PL was positively correlated with strength in mdx (P < .05) but not con. The FA profile in triglyceride showed less difference between groups and far less predictive ability for disease markers. We conclude that profiling the FA composition of tissue lipids (particularly PL) can be a useful strategy for generating novel biomarkers and potential therapeutic targets in muscle diseases and likely other pathological conditions as well. Specifically, the present results have indicated potential benefits of raising content of particular n-3 FAs (especially α-linolenic acid) and reducing content of particular n-6 FAs (linoleic acid) in PL of dystrophic muscle.

摘要

mdx 小鼠是杜氏肌营养不良症的模型。在肌肉营养不良中,脂肪酸(FA)的组成可能会影响疾病的严重程度。我们检测了 mdx 和对照(con)小鼠骨骼肌磷脂(PL)和甘油三酯中的 FA 谱,以评估其与疾病状态的相关性,以及与握力(mdx 中较低)和血清肌酸激酶(CK,mdx 中升高)的相关性。与 con 相比,mdx PL 中二十二碳六烯酸(docosahexaenoic acid,DHA)含量较低(P <.001),亚油酸(linoleic acid,LA)含量较高(P =.001)。DHA 含量与强度或血清 CK 不相关。PL 中的 LA 含量与 mdx 中的 CK 呈正相关(P <.05),但与 con 不相关。PL 中的α-亚麻酸(α-linolenic acid,ALA)含量与 mdx 的强度呈正相关(P <.05),但与 con 不相关。甘油三酯中的 FA 谱在两组之间的差异较小,对疾病标志物的预测能力也较小。我们得出结论,对组织脂质(特别是 PL)的 FA 组成进行分析可以成为一种有用的策略,用于在肌肉疾病和可能其他病理情况下生成新的生物标志物和潜在的治疗靶点。具体而言,本研究结果表明,增加 PL 中特定 n-3 FA(尤其是 ALA)的含量和降低特定 n-6 FA(LA)的含量可能对治疗营养不良性肌肉有益。

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