自噬在Duchenne型肌营养不良中的研究

目的检测Duchenne型肌营养不良症(DMD)患者骨骼肌中LC3和p62的表达情况,分析自噬在DMD骨骼肌细胞坏死中的作用。方法收集2008年1月~2015年5月在我院就诊的病理确诊为DMD的患者(DMD组,81例),另以怀疑为肌病,但肌肉病理未见明显病变者为对照组(6例)。所有入选者均行心肌酶学、肌电图、骨骼肌活检常规组织学和酶学染色、抗dystrophin-N,-C,-R和抗dysferlin免疫组织化学染色。检测其中6例DMD患者及对照组骨骼肌中LC3和p62的表达。结果 81例DMD患者均为男性,起病年龄(4.60±2.35)岁,首发症状多以双下肢起病为主。血清肌酸激酶值的高峰出现在患者年龄的6~8岁,随着肌细胞明显坏死,肌酸激酶水平下降,但仍高于正常。在DMD患者骨骼肌中,组织病理均示典型肌营养不良改变。半定量Western blot提示DMD患者骨骼肌中LC3-II的表达降低,而p62表达显著升高。结论自噬功能障碍可能参与了DMD骨骼肌细胞坏死的病理生理过程。

Role of autophagy in Duchenne muscular dystrophy

Objective To investigate the expression of microtubule-associated protein I light chain 3 (LC3) and p62 in skeletal muscle in patients with Duchenne muscular dystrophy (DMD) and the role of autophagy in necrosis of skeletal muscle cells.Methods A total of 81 patients with pathologically confirmed DMD who visited our hospital from January 2008 to May 2015 were enrolled as DMD group,and 6 patients who were suspected of myopathy and had no marked muscle lesions were enrolled as control group.Myocardial enzyme examination,electromyography,histological and enzymatic staining in skeletal muscle biopsy,and anti-dystrophin-N,-C,-R and antidysferlin immunohistochemical staining were performed for all subjects.The expression of LC3 and p62 in skeletal muscle was measured for 6 DMD patients and the control group.Results All of the 81 DMD patients were male with a mean onset age of 4.60 ± 2.35 years,and the initial symptom was mainly muscle weakness in the lower limbs.Serum creatine kinase reached a peak level at an age of 6 ～8 years and then gradually decreased with increased necrosis of myocytes.Histopathological examination showed typical muscular dystrophy in skeletal muscle in DMD patients.Semi-quantitative Western blot showed a reduction in the expression of LC3-Ⅱ and an increase in the expression of p62 in skeletal muscle in DMD patients.Conclusions Autophagy dysfunction may be involved in the pathophysiological process of skeletal muscle cell necrosis in DMD.