(当前世道很乱,新闻上乱糟糟地,可怜我那些受苦的老人、兄弟、姐妹,憎恨那些不知好歹炫富欺压老百姓的人们。可是,我不是superman,也不是spiderman,其实我更想成为Bruce Li,放倒那些没有良知的家伙,不管你是官、匪还是小混混。但是,我现在什么都不是,只能是花着老百姓的纳税钱,稳定情绪,做好当前实验。为世界劳苦大众祈福。)——自言自语 环境风险因子的毒理学研究,对当前的科研工作者来说,即是挑战也是机遇。如今,毒理学研究已从曾经的传统毒理学研究跨到现代的毒理学研究。传统的毒理学研究更多的是关注半数致死量等宏观指标,而现代毒理学研究开始关注的是低剂量所带来的亚健康以及微观上的基因、蛋白水平的机理性研究。最为重要的是,往往单一因子,单基因、单蛋白的研究开始向多因子暴露,基因组、蛋白组甚至向转录组研究间转化。相信毒理学的非传统研究,特别是联合毒物暴露研究,或许会给我们人类未知病因的疾病带来更多的启示。 下面是一篇有关联合暴露 paper 的报道: 该 study 在小鼠身上发现联合暴露环境毒素可以加速帕金森症患者的神经元退化,且具有年龄相关性。此外,用预处理的抗氧化物质的小鼠明显减弱了环境暴露带来的影响。这就表明联合毒素暴露之所以引起神经退化,是通过氧化应激诱导的。 此研究的 group : One group :婴儿期给予过量的离子 Second group :暴露于除草剂(含有早期对小鼠的帕金森有风险的因子) Third group : 除草剂和过量的离子 Forth group : control 每个组的一半小鼠用抗氧化剂处理,已知这个抗氧化剂能够透过血脑屏障。 目前很多复杂性的疾病,只有很少的一部分被证明是由遗传基因决定的,更多的可能是环境暴露和易感基因 interaction 引起的。 In addition ,又一篇文章证明了研究环境暴露的重要性。空气污染会损伤认知能力,引起抑郁样行为和改变海马细胞因子的表达和形态。 可以看出,联合毒性研究已成为一种趋势,或许会给我们带来更大的回报,有助于我们揭开更多的未知疾病的诱因。 Buck News Combined Exposure to Environmental Toxics Accelerates Age-Related Development of Parkinson's Disease in Mice Buck Institute study highlights the role of environmental factors in the most common form of the neurodegenerative disease June 26, 2007 Scientists at the Buck Institute for Age Research have shown that combining two environmental toxic substances accelerated age-related degeneration in neurons associated with Parkinson’s disease (PD) in mice. Additionally, the study showed that pre-treating the mice with an antioxidant weakened the impact of the environmental exposures, suggesting the substances damage the neurons via oxidative stress. The toxics involved include increased neonatal iron intake and exposure to the herbicide paraquat. Results of the study were published in the June 27 issue of The Journal of Neuroscience . The study highlights the role of environmental factors in the development of PD, a progressive, incurable neurodegenerative disorder that results in tremor, slowness of movement and rigidity. Only five percent of the 160,000 cases of PD diagnosed in the U.S. each year are strictly genetic in nature; most of those afflicted have “sporadic” PD, likely due to a combination of environmental exposures and increased genetic susceptibilities. “Research keeps pointing to Parkinson’s disease as being a very complex disorder,” said Buck Institute faculty member Julie K. Andersen, lead author of the study. “This research looked at environmental risk factors in the context of aging which is essential, given the fact that aging is the single major risk factor for PD in humans.” Andersen and her team worked with genetically identical mice, which put all the animals on the same footing in regards to genetic susceptibility. One group was given an excess of iron in infancy, another was given the herbicide paraquat, (both compounds have been shown to increase the risk of PD in earlier studies in mice), a third group was exposed to both substances and a fourth group was not exposed to either of the compounds. Half of each group received treatment with the antioxidant EUK-189, which is known to cross the blood brain barrier. The animals in each group were aged to the human equivalent of young adult, young middle-age (45 – 55 in humans), young-older (65 – 70 and elderly (85+). Results showed that exposing animals to both toxics accelerated PD-like neurodegeneration in the mice, with symptoms beginning to appear at the human equivalent of middle-age. The mice demonstrated a progression of increased oxidative stress followed by decreased neuronal function and finally neuronal cell loss. In elderly mice, cell loss was roughly equivalent to that observed in the human disorder. Those mice treated with the antioxidant, which was delivered at the same time as the environmental toxic, had significantly less nerve death in the area of the brain commonly affected by PD. “The fact that the antioxidant treatment prevented much of the nerve damage in the mice points to the need for an early diagnostic test for Parkinson’s disease,” said Andersen. “Currently, by the time humans are diagnosed with the disease they have already lost 60% of the neurons implicated in PD; treatment with an antioxidant would likely be maximally effective if taken before symptoms appear in order to halt disease progression." J. Timothy Greenamyre, MD, PhD, Professor of Neurology at the University of Pittsburgh commented on the work, “This study provides further confirmation that ‘innocuous’ early life events or exposures can lead to late life neurodegeneration. Secondly, it adds to the evidence that that abnormalities of iron handling can contribute to the pathogenesis of PD.” He added, “It also shows that early life exposures can predispose to or exacerbate neurodegeneration caused by subsequent exposures.” Joining Andersen in the study were Jun Peng, and Fang Feng Stevensen, also of the Buck Institute, along with Li Peng of the Royal Perth Hospital, Perth, Australia; and Susan R. Doctrow of Proteome Systems, Inc., Woburn, MA. The work was funded by the National Institute of Environmental Health Sciences as part of a large Collaborative Centers for Parkinson’s Disease Environmental Research (CCPDER) U54 grant. The Buck Institute is an independent non-profit organization dedicated to extending the healthspan, the healthy years of each individual’s life. The National Institute of Aging designated the Buck a Nathan Shock Center of Excellence in the Biology of Aging, one of just five centers in the country. Buck Institute scientists work in an innovative, interdisciplinary setting to understand the mechanisms of aging and to discover new ways of detecting, preventing and treating age-related diseases such as Alzheimer’s and Parkinson’s disease, cancer, stroke, and arthritis. Collaborative research at the Institute is supported by genomics, proteomics and bioinformatics technology