“毒奶粉”的毒性与肠道细菌有关 贾伟 我们研究小组对近年来毒奶粉事件中的主角 – “三聚氰胺”在哺乳动物体内的毒性进行了系统研究,结果发表于《科学》 杂志的子刊 《科学 - 转化医学》( Science Translational Medicine 5, 172ra22, 2013 。 相关新闻见: 美国《科学》杂志: Gut Bacteria Conspired in Melamine Poisonings ; 英国《自然》杂志 : Microbes make melamine toxic ; 美国《国家地理》杂志: A New Culprit in China’s Tainted Milk Saga: Gut Bacteria ; Science News: Gut Microbes Could Determine the Severity of Melamine-Induced Kidney Disease ; South China Morning Post: The Chinese milk scandal: Why did some children die and some live ? 三聚氰胺是一种用于制造 塑料、涂料、化肥等化工产品的工业原料。 由于其含氮量高达 67 %左右,近年来被不法厂家添加进牛奶用以增加食品的蛋白质测试含量。在 2008 年下半年发生的中国“毒奶粉”事件中,中国多个省份数万名婴儿因食用被添加了三聚氰胺的奶粉后出现肾结石甚至肾功能衰竭的中毒现象 。其实在这以前三聚氰胺的毒性问题已经“浮出水面”, 2007 年美国发生很多猫和狗的动物中毒死亡的事件,经查这些中毒的动物曾经食用了被添加三聚氰胺的宠物食品,可惜这个情况当时没有引起这些掺假奶粉厂家的重视。 由于三聚氰胺被认为在人体中不吸收,难以单独形成结石,迄今其临床毒性机制一直不甚明了。我们这项研究首次发现了 2008 年中国毒奶粉中的三聚氰胺引发的婴幼儿肾衰竭与肠道细菌的代谢有着密切关系。有些人体内存在少量的肠道微生物(譬如 Klebsiella 属的细菌)具有代谢含氮化合物的(也称为固氮)的能力,能够在肠道中代谢三聚氰胺,将其转化为三聚氰酸并逐步降解。三聚氰胺和三聚氰酸本身毒性极低,但互相极容易结合形成晶体,这两类物质进入血液循环后,在肾小管中与尿酸结合形成大分子复合物类的结石,堵塞肾小管,从而导致肾毒性。 我们在前期研究中发现,由三聚氰胺单一化合物导致的肾毒性大鼠模型的肾脏中有结石形成,同时肠道细菌的代谢产物也发生显著的变化 。因此,我们提出了三聚氰胺的毒性和肠道细菌代谢存在相关性的假说,并在实验中发现三聚氰胺的肾毒性在大鼠肠道细菌通过广谱抗生素抑制时出现显著的下降。体外实验进一步证实三聚氰胺可以被实验动物的粪便中培养出的肠道细菌所降解,这些肠道菌利用三聚氰胺作为氮源进行生物降解,通过连续脱氨基作用逐步形成三聚氰酸二酰胺、三聚氰酸一酰胺、三聚氰酸。我们在种类繁多的肠道细菌中发现 Klebsiella 属的细菌并验证了其对三聚氰胺转化能力,将 Klebsiella 属细菌定植于大鼠的肠道中,发现三聚氰胺的毒性显著增加,肾脏中的结石数目增多。由此明确肠道细菌尤其是 Klebsiella 属能转化三聚氰胺生成三聚氰酸,进而产生结晶而具有肾毒性。我们最后通过肾脏中三聚氰胺、三聚氰酸、尿酸的比例,以及体外重结晶实验,推断出三聚氰胺在肾脏中形成结石的动态过程,即三聚氰胺和三聚氰酸首先结合形成晶核,继而形成三聚氰胺 - 三聚氰酸 - 尿酸的共结晶,结石堵塞肾小管导致肾脏中毒。 人们在日常生活中对饮食、药物的代谢能力和生物反应存在着显著的个体差异,而这些代谢和毒性反应上的个体差异很大程度上可能来自于肠道微生物的差异。相关研究发现,不到 1% 的婴幼儿在食用含三聚氰胺奶粉后出现三聚氰胺所致的肾毒性和泌尿系统疾病,这样的结果提示这一部分婴幼儿之所以发生中毒现象,是由于他们肠道含有较高丰度的能够代谢三聚氰胺的细菌如 Klebsiella 菌的缘故。 三聚氰胺导致的毒奶粉事件虽然过去了,但是在食品及餐具中添加的所谓的“安全物质”以及因人而异的食品中毒现象似乎远远没有得到有效的控制。大约 2-3 周以前新闻报道的新西兰牛奶及奶制品被检测出含有低浓度的化学物质双氰胺(一种与 三聚氰胺 相类似的物质) ,就是当地牧场的农民使用含 双氰胺的 化肥进而使这个物质进入奶牛体内以及我们人类的食物链的一个典型案例。上个月 JAMA Internal Medicine 在线刊出的一篇文章,报道了类似的(或许是更为严重的)一个现象,研究人员让健康志愿者食用仿瓷碗(一种由三聚氰胺为材料制成的 密胺碗)泡 出的热汤面,饭后在志愿者的尿液中检出三聚氰胺。 在我们的环境、食品饮料和药品日益受到各种添加剂影响和化学物质污染的今天,我们需要重新认识“安全性”这个概念。而认识人类自身肠道细菌结构上的不同所带来的代谢上的个体差异,将有助于我们在未来采取更加个性化的药物治疗和营养策略,从根本上有效降低食品和药品中毒的事件。我们希望这项研究能够进一步让人们认识到肠道微生物在食品安全、药物副作用、环境污染等领域所扮演的重要角色。 人体肠道微生物组 (gut microbiome) 的研究工作在国际上方兴未艾,有兴趣的朋友可以阅读曾庆平博主最近的一篇博文《 看不见的“硝烟”看得见的“笑颜”—人体微生物组学研究览胜 》。科学网博主上海交通大学的 赵立平教授 就是在这个竞争异常激烈的新领域较早开展研究工作的科学家之一。近年来我们与赵立平教授、英国帝国理工的 Jeremy Nicholson 教授合作,在肠道菌群代谢产物与人体健康领域开展了一点研究工作,代表性文章如下。 1. Pharmacometabonomic phenotying reveals different responses to xenobiotic intervention in rats. Journal of Proteome Research , 6(4):1364-70, 2007 . 2. Gut microbiota: a potential new territory for drug targeting. Nature Reviews Drug Discovery, 7(2):123-9, 2008. 3. Symbiotic gut microbes modulate human metabolic phenotypes. PROC NATL ACAD SCI USA , 105(6):2117-22, 2008 . 4. Urinary Metabonomic Study on Colorectal Cancer. Journal of Proteome Research , 9(3):1627-34, 2010 . 5. Metabonomic evaluation of melamine-induced acute renal toxicity in rats. Journal of Proteome Research, 9(1), 125-33, 2010 . 6. The footprints of gut microbial-mammalian co-metabolism. Journal of Proteome Research, 10(12):5512-22, 2011 . 7. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME Journal , 6(2):320-9 , 2012 . 8. Host-gut microbiota metabolic interactions. Science , 336(6086): 1262-7, 2012 . 9. Therapeutic modulation of microbiota-host metabolic interactions. Science Translational Medicine , 4(137):137rv6, 2012 . 10. A targeted metabolomic protocol for short-chain fatty acids and branched-chain amino acids. Metabolomics , DOI 10.1007/s11306-013-0500-6 , 2013. 11. Melamine-Induced Renal Toxicity Is Mediated by the Gut Microbiota. Science Translational Medicine , 5, 172ra22 , 2013 .
电解水促进三聚氰胺排泄 来自韩国的研究, 本文的假说是功能水,电解水能促进三聚氰胺中毒后的排泄,为证明这个观点,作者通过建立三聚氰胺中毒动物模型,检测体重、尿液晶体、结石、生物化学和血液学检测、肾脏和膀胱组织学检测等。结果发现,电解水能促进动物的体重增加,同时免疫细胞如淋巴细胞、中性颗粒细胞和单核细胞和脾脏平均重量明显增加。电解水组尿液中晶体显著增加,但膀胱结石形成的几率显著减少。结石的成分 100% 为三聚氰胺。这是国际上首次研究关于电解水可以促进三聚氰胺排泄的研究。 The melamine excretion effect of the electrolyzed reduced water in melamine-fed mice Purchase $ 31.50 Yang-Suk Yoona, 1, Dong-Heui Kima, 1, Soo-Ki Kimb, Soon-Bong Songa, Young Uhc, Dan Jind, Xu-Feng Qia, Yung-Chien Tenga and Kyu-Jae Leea, e, , a Department of Environmental Medical Biology, Wonju College of Medicine, Yonsei University, Wonju, Gangwon 220-701, Republic of Korea b Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju, Gangwon 220-701, Republic of Korea c Department of Laboratory Medicine, Wonju College of Medicine, Yonsei University, Wonju, Gangwon 220-701, Republic of Korea d Department of Immunology and Pathogenic Biology, College of Medicine, Yanbian University, Yangi, Jilin 133000, China e Institute for Poverty Alleviation and International Development, Yonsei University Wonju Campus, Wonju, Gangwon 220-710, Republic of Korea Received 5 February 2011; accepted 26 April 2011. Available online 5 May 2011. Abstract Our hypothesis is that the intake of functional water, electrolyzed reduced water (ERW) can excrete melamine in body was evoked by melamine-tainted feed (MTF). To address this issue, we investigated the effect of ERW in MTF-mice model by way of body weight gain, incidence of urinary crystals and bladder stone, biochemical and haematological examination, histopathologic finding of kidney and urinary bladder, and the evaluation of bladder stone. We found that the rate of body weight gain was significantly more increased in MTF + ERW group than MTF + PW group. Accordingly, the number of immunocytes such as leukocyte, neutrophil and monocyte as well as the mean weight of spleen was significantly increased in MTF + ERW group. The incidence of urinary crystals was significantly higher in MTF + ERW group, whereas the incidence of urinary bladder stones was lower in MTF + ERW group (52.4%) than in MTF + PW group (38.1%). Also, urinary crystals were more precipitated in MTF + ERW group than MTF + PW group, and urinary bladder stone consists of 100% melamine. Collectively, our data clearly show that ERW intake is helpful to excrete of melamine in MTF mice model and this is the first report on the melamine excretion and clinically implying the safer fluid remedy for melamine-intoxicated hosts.
在很长一段时间内,美国一直在与前苏联争夺着外层空间的霸主地位。今天,美国再次卷入了一场别开生面战役:国际新兴纳米技术领域主导地位的较量,即在原子尺度上研究物质,进而研发新型材料。参加两周后即将开幕的 2010中国(上海)国际纳米展览会 的代表将更为清楚地认识到,中国将紧紧跟随美国的脚步,并最终成为纳米技术领域的领跑者。 中国可以赶超美国并最终超越其他所有竞赛者并非天方夜谭:中国在纳米技术领域的投入在 过去十年中每年以20% 的速度增长。现在,中国在纳米技术领域的文章数量比任何其他国家都要多,而且近年来,中国在这一领域获得的专利许可数量已经超过了美国。美国在纳米技术领域的投入 每年以18%的速度增长 ,照此看来,尽管美国在投入方面依旧会处于领先地位(2008年的研发投入是57亿美元),但是其他竞赛者,特别是中国,正在高速追赶。也正是由于这个原因,在 总统科技顾问委员会给美国总统奥巴马的一份报告 中指出,美国应加大对纳米技术领域的投资。 纳米技术具有广泛的应用,包括医学、军事、环境整治、工程以及生活消费品生产等等领域,据测截至2012年产业效益可以达到2万亿。这也是为什么各国在这个领域内投入如此之高,而且在竞争中如此激烈角逐的原因,每个国家都力争在这场战役中脱颖而出。 中国已经在纳米技术领域取得了一些成绩,例如纳米扬声器,去年 卫报 报道的一个只有一毫米厚的音频系统。然而对于中国制造的纳米产品的质量问题,业内专家还是存在一定的质疑。 英国纳米技术协会 的Mark Morrison博士指出,来自中国科研机构的同行评审学术论文的引用次数要远远少于来自美国、日本的欧盟国家的。他还 指出 了这一行业中健康、安全以及生产标准的重要性:我们(英国)恪守标准,也许这看起来很枯燥,但是它对于纳米技术的发展以及环境、健康和安全方面的研究是至关重要的。 不可否认的是,适当的安全标准和质量控制措施对于产品安全投放到市场是至关重要的。 去年八月 在中国某家纳米技术生产工厂里两位年轻女性的死亡以及五例致病案例为行业安全生产规范敲响了警钟。尽管没有确凿的证据表明死者的死因是其所接触的纳米颗粒所致,但是据调查工厂内并没有执行可以预防潜在伤害的标准生产安全规范。 在纳米技术领域以外,类似的案例如 婴儿奶粉中添加三聚氰胺 等事件的出现,也会加剧人们对中国纳米产品质量的怀疑。如果中国政府能够和国内的纳米科学家、科学工作者以及企业家一道,像发达国家一样切实落实并加强行业标准和规范,中国在纳米技术领域的投入将有可能得到更为丰厚的回馈。仅仅赢得竞争是不够的,关键是要摘掉不合格的帽子。 原文: China poised to take the lead in nanotechnology For many years the US was involved in a space race with the Soviet Union, a competition to see who could be the first to explore the outer reaches of space. Now, the US is embroiled in a different kind of battle: the race to dominate the emerging international industry surrounding nanotechnology, the manipulation of matter on an atomic scale to develop new materials. As will become clear to delegates at the Nanotech China meeting in Shanghai in just two weeks, China has positioned itself hot on the heels of the US and is poised to take the lead in the race for domination of the industry. Chinas ability to catch up with the US and pass all other participants in the race should not come as a surprise: its investment in nanotech has increased by 20% every year for the past decade . As a result, China now produces more papers on nanotech than any other country, and it has surpassed the US in recent years in the number of nanotech patents granted. At the same time, investment in nanotech in the US grew at a rate of 18% per year , with the result that, although the US still leads the way in terms of investment (with Research and Development investments of $5.7 billion in 2008), the rest of the world, and especially China, is rapidly catching up. This is the basis of a report to President Obama from the President's Council of Advisors on Science and Technology calling for increased investment in the sector. Nanotechnology, which has very broad applications including uses in medicine, the military, environmental management, engineering and the manufacture of consumer goods, is predicted to represent a two-trillion-dollar industry by 2012. This explains the high levels of investment in this sector and why countries are jostling for the lead in the race, as each of them strives for an edge in global competitiveness. China has already had some success in the area of nanotech; for example, the nano-speaker, a one-millimetre-thick audio speaker reported in the Guardian last year. However, this success is not without controversy, and there have been some questions from industry experts regarding the quality of nanotech products coming out of China. Dr Mark Morrison of the Institute of Nanotechnology in Scotland has made the point that Peer-reviewed scientific papers from Chinese institutes are cited far less than those from US, Japan and EU. He also pointed to the importance of health and safety as well as manufacturing standards for the industry: We are strong in standards, which may seem boring, but is critical to the development of nanotechnology and environment, health and safety research. It is undeniable that appropriate safety regulations and quality control procedures will be critical for products to reach the market. The deaths of two young women and illnesses of five others in August last year , while working in a Chinese nanotech manufacturing facility, strengthen the need for caution and tight regulations in the industry. However, the cause of death has not been definitively attributed to the nanoparticles the women were exposed to, and standard manufacturing safety practices that could have prevented any harm were not being observed in the factory. Stories such as this and other, non-nanotech-related scandals like the melamine in baby milk incident will serve to foster scepticism and questions regarding nanotechnology products emerging from China. If the Chinese government, working together with Chinese nanotechnologists, scientists and business leaders, could implement and enforce standards and regulations similar to those established elsewhere in the developed world, its investment in the sector will be far more likely to bear fruit in the future. It is not enough just to win the race; one must also avoid disqualification. Thin-film nano speaker over the screen of an IPod: