X-连锁肾上腺脑白质营养不良患者成纤维细胞系MnSOD基因表达增强

Gene expression of MnSOD in X-linked Adrenoleukodystrophy fibroblasts X-ALD murine model

探讨X 连锁肾上腺脑白质营养不良 (X linkedAdrenoleukodystrophy,X ALD)个体的MnSOD表达的变化与发病机理的相关性。应用免疫组化、免疫荧光、定量PCR法 ,观察锰过氧化物岐化酶 (Mnactivatedsuperoxidedismutase ,MnSOD)表达的差异。免疫组化的结果显示X ALD小鼠脑组织中MnSOD的含量高于野生型小鼠 ;免疫荧光显示CCER(X ALD中最严重的一种 )患者成纤维细胞中的MnSOD含量高于健康人 ;定量PCR显示CCER患者成纤维细胞中MnSODmRNA量高于健康人 ,并且MnSOD能被 4PBA诱导。推测氧化应激升高可能是造成X ALD患者神经系统退行性改变的原因之一。而MnSOD增加则有助于细胞清除氧自由基 ,缓解氧化应激 ,为应用 4PBA治疗X

These studies focus on the metabolic defect and pharmacological therapies of X linked adrenoleukodystrophy (X ALD). There are several indications that oxidative stress is likely to play a role in pathophysiology of X ALD. In this research, immunohistochemical studies showed that Mn activated superoxide dismutase (MnSOD) was increased in the brain of X ALD mouse. Immunofluorescent studies showed that there is more detectable MnSOD in fibroblasts from CCER (severe form of X ALD) patients and quantitative PCR showed that MnSOD mRNA was increased in fibroblasts from CCER patients and expression of MnSOD was induced by 4PBA. This is a first report that X ALD is associated with oxidative stress. Enhancing expression of MnSOD by 4PBA may be helpful to inner cellular environment amelioration and thus become an approach to treat X ALD.