Abdel Salam E, Abdel-Meguid I, Korraa S
Department of Pediatrics, Genetic Unit, Faculty of Medicine, Cairo University.
Acta Myol. 2007 Jul;26(1):14-21.
Replicative aging and oxidative stress are two plausible theories explaining the etiology of muscular dystrophy. The first theory indicates that replicative aging of myogenic cells (satellite cells), owing to enhanced myofiber turnover, is a plausible explanation of the progression of Duchenne muscular dystrophy (DMD). The oxidative stress theory indicates that failure of muscle regeneration to keep up with the ongoing apoptosis and necrosis following oxidative stress, that normally associates muscular exercise, leads to muscle atrophy in DMD. To test for these two theories, markers of replicative aging and oxidative stress were assessed in the blood of 30 DMD patients vs. 20 normal healthy age matching controls. Markers of replicative aging showed significantly lower telomerase activity, significantly increased expression of receptors for advanced glycation end products (RAGEs) mRNA and Bax mRNA (an apoptotic gene) in DMD compared to controls. There was a significant increase in markers of oxidative stress among DMD patients compared to controls, measured in terms of increased apoptotic percentage in circulating mononuclear cells, increased lipid peroxidation measured in terms of plasma malondialdehyde (MDA) and increased protein carbonyls. Levels of plasma nitric oxide (NO), which neutralizes oxygen radicals, and expression of inducible nitric oxide synthase (iNOS) mRNA in neutrophils was significantly lower among DMD compared to controls. Biostimulation of WBC by helium neon (He:Ne) laser irradiation induced a significant increase in the expression of iNOS mRNA and plasma NO levels, but still at a lower level compared to controls. He:Ne laser irradiation induced a marked decrease in markers of oxidative stress among DMD patients compared to their level before irradiation, measured in terms of decreased plasma protein carbonyls, decreased plasma MDA, and decreased apoptosis percentage.
This study points to that oxidative stress is the prime cause for muscle degeneration in DMD and points out to the possible ameliorative effect of He:Ne laser on this
复制性衰老和氧化应激是解释肌肉萎缩症病因的两种合理理论。第一种理论表明,由于肌纤维更新增强,成肌细胞(卫星细胞)的复制性衰老可能是杜兴氏肌肉萎缩症(DMD)进展的一种合理解释。氧化应激理论表明,肌肉再生未能跟上氧化应激后持续的细胞凋亡和坏死(氧化应激通常与肌肉运动相关),导致DMD患者出现肌肉萎缩。为验证这两种理论,在30例DMD患者和20例年龄匹配的正常健康对照者的血液中评估了复制性衰老和氧化应激的标志物。与对照组相比,DMD患者的复制性衰老标志物显示端粒酶活性显著降低,晚期糖基化终产物受体(RAGEs)mRNA和Bax mRNA(一种凋亡基因)的表达显著增加。与对照组相比,DMD患者的氧化应激标志物显著增加,以循环单核细胞凋亡百分比增加、血浆丙二醛(MDA)测量的脂质过氧化增加以及蛋白质羰基增加来衡量。与对照组相比,DMD患者中中和氧自由基的血浆一氧化氮(NO)水平以及中性粒细胞中诱导型一氧化氮合酶(iNOS)mRNA的表达显著降低。氦氖(He:Ne)激光照射对白细胞的生物刺激导致iNOS mRNA表达和血浆NO水平显著增加,但仍低于对照组。与照射前相比,He:Ne激光照射使DMD患者的氧化应激标志物显著降低,以血浆蛋白质羰基降低、血浆MDA降低和凋亡百分比降低来衡量。
本研究指出氧化应激是DMD肌肉退化的主要原因,并指出He:Ne激光对此可能具有改善作用。