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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

张紫玲, 陆茜, 徐登球, 俞沁玮, 江振洲

张紫玲, 陆茜, 徐登球, 俞沁玮, 江振洲. 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[J]. 中国药科大学学报, 2021, 52(6): 735-741. DOI: 10.11665/j.issn.1000-5048.20210612
引用本文: 张紫玲, 陆茜, 徐登球, 俞沁玮, 江振洲. 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[J]. 中国药科大学学报, 2021, 52(6): 735-741. DOI: 10.11665/j.issn.1000-5048.20210612
ZHANG Ziling, LU Qian, XU Dengqiu, YU Qinwei, JIANG Zhenzhou. Effect and mechanism of muscle injury on liver lipid metabolism in Duchenne muscular dystrophy mice[J]. Journal of China Pharmaceutical University, 2021, 52(6): 735-741. DOI: 10.11665/j.issn.1000-5048.20210612
Citation: ZHANG Ziling, LU Qian, XU Dengqiu, YU Qinwei, JIANG Zhenzhou. Effect and mechanism of muscle injury on liver lipid metabolism in Duchenne muscular dystrophy mice[J]. Journal of China Pharmaceutical University, 2021, 52(6): 735-741. DOI: 10.11665/j.issn.1000-5048.20210612

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

基金项目: 国家自然科学基金资助项目(No.81773827);江苏省第十四批“六大人才高峰”高层次人才资助项目(No.SWYY-094);“双一流”团队:药物安全预警关键技术研究创新团队资助项目(No.CPU2018GY33);江苏省研究生科研与实践创新计划资助项目(No.KYCX19_0763)

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

Funds: This study was supported by the National Natural Science Foundation of China (No.81773827), the Scholar of the 14th batch of "Six Talents Peak" High-Level Talent Selection (No.SWYY-094), the "Double First-Class" University Project (No.CPU2018GY33), and the Postgraduate Research Practice Innovation Program of Jiangsu Province (No.KYCX19_0763)
  • 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.
  • [1] . Liver Int,2021,41(4):683-691.
    [2] Fan LY,Sweet DR,Prosdocimo DA,et al. Muscle Krüppel-like factor 15 regulates lipid flux and systemic metabolic homeostasis[J]. J Clin Invest,2021,131(4):e139496.
    [3] Moon JS,Yoon JS,Won KC,et al. The role of skeletal muscle in development of nonalcoholic fatty liver disease[J]. Diabetes Metab J,2013,37(4):278-285.
    [4] Srikanthan P,Hevener AL,Karlamangla AS. Sarcopenia exacerbates obesity-associated insulin resistance and dysglycemia:findings from the National Health and Nutrition Examination Survey III[J]. PLoS One,2010,5(5):e10805.
    [5] Huang JS,Glauber M,Qiu ZH,et al. The influence of skeletal muscle on the regulation of liver:body mass and liver regeneration[J]. Am J Pathol,2012,180(2):575-582.
    [6] Van Der Windt DJ,Sud V,Zhang HJ,et al. The effects of physical exercise on fatty liver disease[J]. Gene Expr,2018,18(2):89-101.
    [7] Takahashi H,Kotani K,Tanaka K,et al. Therapeutic approaches to nonalcoholic fatty liver disease:exercise intervention and related mechanisms[J]. Front Endocrinol (Lausanne),2018,9:588-604.
    [8] Duan D,Goemans N,Takeda S,et al. Duchenne muscular dystrophy[J]. Nat Rev Dis Primers,2021,7(1):13-32.
    [9] Cirak S,Feng L,Anthony K,et al. Restoration of the dystrophin-associated glycoprotein complex after exon skipping therapy in Duchenne muscular dystrophy[J]. Mol Ther,2012,20(2):462-467.
    [10] Nathwani RA,Pais S,Reynolds TB,et al. Serum alanine aminotransferase in skeletal muscle diseases[J]. Hepatology,2005,41(2):380-382.
    [11] White Z,Hakim CH,Theret M,et al. High prevalence of plasma lipid abnormalities in human and canine Duchenne and Becker muscular dystrophies depicts a new type of primary genetic dyslipidemia[J]. J Clin Lipidol,2020,14(4):459-469.
    [12] Jeon BN,Kim YS,Choi WI,et al. Kr-pok increases FASN expression by modulating the DNA binding of SREBP-1c and Sp1 at the proximal promoter[J]. J Lipid Res,2012,53(4):755-766.
    [13] Wakil SJ,Abu-Elheiga LA. Fatty acid metabolism:target for metabolic syndrome[J]. J Lipid Res,2009,50 SupplS:138-143.
    [14] Mei Lk,Wei QQ,Zhang HB,et al. Research progress in acetyl-CoA carboxylase inhibitors[J] J China Pharm Univ(中国药科大学学报),2019,50(3):253-264.
    [15] Abu-Elheiga L,Almarza-Ortega DB,Baldini A,et al. Human acetyl-CoA carboxylase 2. Molecular cloning,characterization,chromosomal mapping,and evidence for two isoforms[J]. J Biol Chem,1997,272(16):10669-10677.
    [16] Chen GX,Liang GS,Ou J,et al. Central role for liver X receptor in insulin-mediated activation of Srebp-1c transcription and stimulation of fatty acid synthesis in liver[J]. Proc Natl Acad Sci U S A,2004,101(31):11245-11250.
    [17] Schomaker S,Potter D,Warner R,et al. Serum glutamate dehydrogenase activity enables early detection of liver injury in subjects with underlying muscle impairments[J]. PLoS One,2020,15(5):e0229753.
    [18] Wagner KR. The elusive promise of myostatin inhibition for muscular dystrophy[J]. Curr Opin Neurol,2020,33(5):621-628.
    [19] Dasarathy S. Cause and management of muscle wasting in chronic liver disease[J]. Curr Opin Gastroenterol,2016,32(3):159-165.
    [20] Garcia PS,Cabbabe A,Kambadur R,et al. Brief-reports:elevated myostatin levels in patients with liver disease:a potential contributor to skeletal muscle wasting[J]. Anesth Analg,2010,111(3):707-709.
    [21] Hanai T,Shiraki M,Ohnishi S,et al. Rapid skeletal muscle wasting predicts worse survival in patients with liver cirrhosis[J]. Hepatol Res,2016,46(8):743-751.
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出版历程
  • 收稿日期:  2021-05-17
  • 修回日期:  2021-10-27
  • 刊出日期:  2021-12-24

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