Hunter Randy L, Liu Mei, Choi Dong Young, Cass Wayne A, Bing Guoying
Department of Anatomy and Neurobiology, University of Kentucky, Lexington KY 40536-0098, USA.
Curr Aging Sci. 2008 Jul;1(2):112-21. doi: 10.2174/1874609810801020112.
Evidence suggests chronic inflammation and iron accumulation may play a role in the pathogenesis of Parkinson's disease (PD) as inflammation and iron levels increase with age and appear in the disease pathology. It is hypothesized that an aggravated inflammatory response and iron accumulation, as a function of age, increase oxidative stress and participate in the pathogenesis of PD. Intracranial injection of the bacterial endotoxin, lipopolysaccharide (LPS), has been shown to induce microglia activation, oxidative stress, mitochondrial impairment, iron accumulation, and dopaminergic neurodegeneration within the substantia nigra. We tested the hypothesis that injection of LPS into the striatum would increase iron accumulation in the substantia nigra of aged rats compared to young ones. Our results showed that four weeks post injection, LPS significantly increased microglia activation, lipid peroxidation, ferritin expression, and total nigral iron content in aged rats. In addition, LPS significantly altered the turnover ratio of homovanillic acid to dopamine. Thus, an age-related increase in iron as well as susceptibility to inflammation may play an important role in PD-related neurodegeneration, as free radicals produced from the inflammatory response can become more toxic through increased ferrous iron catalyzed Fenton chemistry. This may enhance oxidative stress, exacerbate microglia activation, and drive the progression of PD.
有证据表明，慢性炎症和铁蓄积可能在帕金森病（PD）的发病机制中起作用，因为炎症和铁水平会随着年龄增长而升高，并出现在疾病病理过程中。据推测，随着年龄增长，炎症反应加剧和铁蓄积会增加氧化应激，并参与PD的发病机制。颅内注射细菌内毒素脂多糖（LPS）已被证明可诱导黑质内的小胶质细胞活化、氧化应激、线粒体损伤、铁蓄积和多巴胺能神经元变性。我们检验了这样一个假设：与年轻大鼠相比，向纹状体内注射LPS会增加老年大鼠黑质中的铁蓄积。我们的结果表明，注射后四周，LPS显著增加了老年大鼠的小胶质细胞活化、脂质过氧化、铁蛋白表达和黑质总铁含量。此外，LPS显著改变了高香草酸与多巴胺的周转率。因此，与年龄相关的铁增加以及对炎症的易感性可能在与PD相关的神经变性中起重要作用，因为炎症反应产生的自由基可通过增加亚铁催化的芬顿化学反应而变得更具毒性。这可能会增强氧化应激，加剧小胶质细胞活化，并推动PD的进展。
