CAJ | 학술논문

目的：杜氏进行性肌营养不良症（duchenne muscular dystrophy，DMD）是最常见的肌营养不良症，目前尚无药可医。以往的表达谱研究很少将疾病样本分阶段进行分析。本研究的目的是整合基因表达谱数据库（gene ex-pression omnibus，GEO）中的 DMD 相关的表达谱数据，根据不同发病阶段进行分析，以期望揭示新的发病机制，为以后的诊疗研究提供可靠的靶标。方法我们利用从 GEO 数据库下载的两套表达谱芯片的数据（GSE6011和 GSE3307）针对 DMD 不同疾病阶段进行了差异表达基因分析和通路富集分析。结果在症状发生前样本中，我们鉴别出41个富集了差异表达基因的通路；在症状发生后的样本中，我们鉴别出33个通路。70％的通路是这两个阶段共有的，且大部分与免疫相关。进一步的分析发现症状发生前的患者在肌肉重建和维持心肌细胞钙平衡方面的表现优于症状发生后的患者。神经元型一氧化氮合酶（Neuronal nitric oxide synthase，NOS）、二氢吡啶受体（dihydropyridine receptors， DPHR）、肌质／内质网钙腺苷三磷酸酶（sarcoplasmic ／endoplasmic reticulum calcium ATPase，SERCA）和受磷蛋白（phos-pholamban，PLN）有希望成为以后诊断治疗靶标。结论我们的研究为进一步了解 DMD 的发病机制奠定了基础。
목적：두씨진행성기영양불량증（duchenne muscular dystrophy，DMD）시최상견적기영양불량증，목전상무약가의。이왕적표체보연구흔소장질병양본분계단진행분석。본연구적목적시정합기인표체보수거고（gene ex-pression omnibus，GEO）중적 DMD 상관적표체보수거，근거불동발병계단진행분석，이기망게시신적발병궤제，위이후적진료연구제공가고적파표。방법아문이용종 GEO 수거고하재적량투표체보심편적수거（GSE6011화 GSE3307）침대 DMD 불동질병계단진행료차이표체기인분석화통로부집분석。결과재증상발생전양본중，아문감별출41개부집료차이표체기인적통로；재증상발생후적양본중，아문감별출33개통로。70％적통로시저량개계단공유적，차대부분여면역상관。진일보적분석발현증상발생전적환자재기육중건화유지심기세포개평형방면적표현우우증상발생후적환자。신경원형일양화담합매（Neuronal nitric oxide synthase，NOS）、이경필정수체（dihydropyridine receptors， DPHR）、기질／내질망개선감삼린산매（sarcoplasmic ／endoplasmic reticulum calcium ATPase，SERCA）화수린단백（phos-pholamban，PLN）유희망성위이후진단치료파표。결론아문적연구위진일보료해 DMD 적발병궤제전정료기출。
Objective To explore the pathogenesis of Duchenne muscular dystrophy (DMD) by integrating microarray data related with DMD from Gene Expression Omnibus (GEO)database and to analyze these data.Methods The differential expression gene analysis and pathway enrichment analysis were performed by means of the two datasets,GSE6011 and GSE3307 that were downloaded from GEO database.Results In the specimens before symptom onset were identified as 41 pathways that were rich with differential expression genes and 33 pathways in the specimens after symptom onset in which 70% of pathways were shared in both phases,furthermore,most of them were correlated to immunity.Further investigation showed that presymptomatic patients were superior to post -symptomatic patients in the respects of muscle regeneration and calcium homeostasis maintaining in myocardial cell.Neuronal nitric oxide synthase (NOS ),dihydropyridine receptors (DHPR),sarcoplasmic /endoplasmic reticulum calcium ATPase (SERCA)and phospholamban (PLN)might become potential targets for molecular diagnostic tests and treatment of DMD in the future.Conclusion The experimental results provide a basis for understanding further the pathogenesis of DMD.