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杜氏肌营养不良小鼠肌损伤对肝脏脂质代谢的影响及其作用机制

Effect and mechanism of muscle injury on liver lipid metabolism in Duchenne muscular dystrophy mice

  • 摘要: 杜氏肌营养不良(Duchene muscular dystrophy,DMD)是一种严重的进行性肌肉萎缩性疾病,近年来关于其患者脂质异常的报道增多,但对其肝脏脂质的关注不多。本实验旨在探究抗肌萎缩蛋白的基因缺陷对肝脏脂质合成产生的影响。以7周龄的mdx雄性小鼠为DMD模型,通过肝脏组织形态学检查、血生化检测,以及基因和蛋白表达量检测,考察肝功能、肝脏脂质蓄积、肝脏脂质合成情况。实验结果显示,mdx小鼠肝脏脂滴明显增多,肝脏内总胆固醇、甘油三酯含量上升,血清中天冬氨酸转氨酶、丙氨酸转氨酶以及总胆汁酸含量上升。脂质合成相关酶中的脂肪酸合成酶、乙酰辅酶A羧化酶、胆固醇调节元件结合蛋白1-c的基因与蛋白表达量均有上调。实验结果表明7周龄mdx雄性小鼠肝脏存在脂质蓄积。

     

    Abstract: Duchene muscular dystrophy (DMD) is a serious progressive muscular dystrophy.Reports in recent years about abnormal lipid in DMD patients have increased, yet little attention has been paid to liver lipid.This study aimed to explore the effect of dystrophin gene defect on liver lipid synthesis.7-week-old mdx male mice were used as DMD model.The conditions of liver function, liver lipid accumulation and liver lipid synthesis were determined through liver tissue morphological examination, blood biochemical examination, and detection of hepatic gene and protein expression.The results showed that lipid droplets in liver of mdx mice increased significantly.The contents of total cholesterol and triglyceride in liver, aspartate aminotransferase and alanine aminotransferase in serum increased.The gene and protein expression of hepatic lipid synthesis-related enzymes such as fatty acid synthase, acetyl CoA carboxylase, and sterol regulatory element binding protein 1-c were up-regulated.These results showed accumulation of liver lipid in 7-week-old mdx male mice.

     

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