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一条小鱼可以拯救你的听力?

时间:2010-07-29 13:07    来源:    作者: 点击:
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    For many people, loss of hearing is irreversible.

    For scientists trying to figure out what can be done about that, one answer may lie -- or swim, actually -- in freshwater aquariums.

    About one of every 10 Americans suffers from hearing impairment, according to a survey conducted by the Better Hearing Institute, a nonprofit advocacy group. By far the most common cause of hearing loss is damage to the so-called hair cells in the inner ear as a result of excessive noise, certain illnesses and drugs, and simple aging. The problem is that once hair cells die, humans (like other mammals) aren't able to grow new ones.

    In recent years, a research team at the University of Washington in Seattle has been working on finding a way to resolve that problem in experiments involving the zebrafish, a common aquarium denizen. The zebrafish, like many aquatic creatures, has clusters of hair cells running along the outside of its body that help sense vibrations in the water, working in a similar way to hair cells in the human inner ear. But unlike humans, zebrafish are able to regenerate their damaged hair cells. Researchers hope their work can unlock secrets to protect human hair cells from becoming damaged and to stimulate the cells to regenerate.

    Hair cells, which took their name because under the microscope they look like cells with little hairs growing out of them, are an essential link in hearing. The filament hairs, or cilia, bend with vibrations caused by sound waves entering the ear. That induces the hair cell to create an electrical signal that is passed on to the auditory nerve and sent to the brain. Devices such as hearing aids, which amplify sounds, and cochlear implants, which stimulate the auditory nerve directly, help people hear, but neither restores hearing to normal.

    Until the mid-1980s, researchers thought warm-blooded vertebrates, including humans, weren't able to regenerate hair cells. Then, researchers around the country began observing that hair cells grew back in birds whose hearing was damaged either by noise or drugs. They also determined that hair-cell regeneration can result in improved hearing; in experiments, song birds that had grown new hair cells were able to resume singing their original songs with perfect pitch again.

    But there is no indication that mammals can regenerate hair cells. And why some animals, even within the same species, are more vulnerable to hair-cell death, while others are more resistant to it, is a mystery. 'I literally walked around for years wondering about this variability,' says Ed Rubel, a professor of hearing sciences who leads part of the University of Washington research effort.

    There are two main approaches to efforts aimed at inducing hair cells to regenerate. Some research groups are attempting to get stem cells -- undifferentiated cells that can develop into various specialized cells -- to turn into hair cells, either by transplanting them from other parts of the body, or by stimulating stem cells naturally occurring in the inner ear to transform themselves. Albert Edge, an associate professor at Harvard Medical School and a researcher at the Massachusetts Eye and Ear Infirmary, says his team has been able to turn mouse stem cells into hair cells in a laboratory dish, though it isn't clear whether those cells are functional or not.

    Other researchers, like those at the University of Washington, are focused on understanding the molecules and genetics involved with hair-cell regeneration, and how to mimic this process in animals that don't spontaneously regenerate hair cells. Scientists say aspects of such research, likely will be the first to have applications in humans. One encouraging angle: Dr. Rubel, in collaboration with another University of Washington scientist, David Raible, has identified chemicals that seem to protect hair cells from damage. In this experiment, zebrafish are exposed to a dye that highlights living hair cells. Then, one or two of the zebrafish -- the young ones used in the lab measure just 1/8 of an inch long -- are placed in each of 96 shallow holes contained on a plate. Different chemicals are administered to each fish group that might confer protection to the hair cells.

    Finally, another chemical known to kill the fish hair cells is added. Under a microscope, researchers then examine the fish to look for cases where the dye is still evident, signaling that the cells are still alive and suggesting that the protective chemical appears to have done its job.

    Those chemicals found to confer protection on fish hair cells are currently also being tested on mice and rats. The idea is that, once a drug is discovered that effectively protects hair cells from dying and is safe for humans, the medicine could be used to help protect the hearing of patients receiving drugs known for killing hair cells, like chemotherapeutic agents.

    Dr. Rubel's and Dr. Raible's teams also are studying the genetics of zebrafish to identify markers that confer hair-cell protection.

    Last year, their labs jointly identified several genetic mutations and drug-like compounds that seemed to protect hair cells from death, publishing their findings in the journal PLoS Genetics. In a separate study, published in 2007 in Hearing Research, they identified several drugs that also appear to be protective and were already approved for other purposes by the Food and Drug Administration. No tests have been performed on humans, however.

    The teams also are working on a separate group of studies to understand the genes and other molecules that allow the regeneration of hair cells in zebrafish, birds and mice.

    Surrounding cells known as support cells can both turn into hair cells or generate new hair cells. Dr. Rubel's lab is investigating both processes. 'If we understand the template of genes that are expressed by the cells we would want to divide, then we could tap into that template' to mimic regeneration efforts in mammals, he says.

    One finding identified a developmental protein that appears to be turned on in animals able to regenerate hair cells. In one study, a team member found a type of protein increased in a chick (which can regenerate hair cells) after its cells were damaged. But in running the same experiment in a mouse (which can't regenerate hair cells), the protein didn't increase, suggesting the protein could be involved in regeneration.

    Scientists involved in the experiments say there could be therapeutic trials to prevent hearing loss using drugs within a decade. However, finding a cure for hearing loss using hair-cell regeneration is likely to be at least 20 years away, they say.

    'Hearing aids are Band-aids on a problem that already exists,' says Nancy Freeman, director of the regenerative and development program in hearing loss at the National Institute on Deafness and Other Communication Disorders.

    'The hope with this type of [regeneration] approach is that at the end of the day you'd end up with something that natively restores function.'

    对良多人来讲,听力的损失踪是一件无法挽回的事。

    对致力于研究这一题目的科学家来说,休止听力损失踪的一个步伐可以在淡水水族馆里找到。

    在放年夜2.1万倍的照片中可以清楚明明的看到耳蜗内的"毛细胞"非营利构造改进听力协会(Better Hearing Institute)的一项查询拜访剖明,约莫每10个美国人中就有一人患有听力窒碍。到今朝为止,听力损失踪最常见的缘故起因便是内耳中所谓的"毛细胞"受到侵害可能仅仅是由于上了岁数。过量的噪音以及某些疾病和药物会侵害毛细胞。题目的症结在于毛细胞一旦衰亡,人类(像其他哺乳动物一样)不能再生出新的毛细胞。

    连年来,华盛顿年夜学西雅图分校的一个研究团队一向在对一种水族馆里常见的不雅鉴赏鱼类──斑马鱼举办研究,试图办理人类听力损失踪的题目。和良多其他水生生物一样,斑马鱼在身材外貌长有毛细胞。这些毛细胞的浸染是探测水中的振动,其事理与人类内耳中的毛细胞相似。可是,与人类差此外是,斑马鱼的毛细胞在受损后还可以再生。研究职员但愿他们的事项可以揭开答案,掩护人类的毛细胞免受损伤、并敦促毛细胞的再生。

    内耳中的这种细胞是人类听觉不成或缺的一环。之以是称为"毛细胞",是由于它们在显微镜下看上去就像是在细胞外长出了绒毛。这些细细的绒毛,可能说纤毛,会由于声波进中听朵往后孕育产生的振动而摆动。这种行为会让毛细胞孕育产生出一种能够经过听觉神经传给年夜脑的电旌旗灯号。像助听器和人工耳蜗等配置都有助听下场,但都无法让人们的听力规复到正常水平。助听器能够增进声音的强度,而人工耳蜗则会直接刺激听觉神经。

    上世纪80年代中期过去,研究职员以为毛细胞无法在包孕人类在内的温血脊椎动物的体内再生。厥后,美国的研究职员起头仔细到,鸟类的听力在因噪音或药物受损后,它们的毛细胞会从头再生出来。研究者们还认定,毛细胞再生可以进步听力。尝试发明,新长出毛细胞的鸣禽可以从头以美满的调子唱出它们畴前的歌曲。

    可是,没有迹象剖明哺乳动物的毛细胞可以再生。另外,即便在同一物种中,为什么某些动物的毛细胞更轻易衰亡,而某些动物的毛细胞却生命力更执拗,这模仿仍是是一个谜。"这些年来,我真的乃至在走路的时辰都在思考为什么会有这个差别,"听力科学教授埃德?鲁贝尔(Ed Rubel)说。鲁贝尔认真率领华盛顿年夜学科研项目的一部分事项。

    促进毛细胞再生首要有两种步伐。有些研究构造正在试图将干细胞──一种未特化的细胞,它可以特化出其余范例细胞──培育种植抬举成为毛细胞。要领是将它们从身材的其余部位移植,可能促使内耳里自然发展的干细胞产生改变,特化为毛细胞。阿尔伯特?埃奇(Albert Edge)是哈佛年夜学医学院(Harvard Medical School)的副教授,也是麻省病院眼耳科(Massachusetts Eye and Ear Infirmary)的研究职员。埃奇暗示,他的团队已经能够在尝试室中将老鼠的干细胞解析成毛细胞,可是此刻还不清楚明明这些细胞是否能够正常事项。

    而华盛顿年夜学等构造的其他研究职员则将仔细力齐集在同毛细胞再生有关的分子和遗传学事理,以及怎样在毛细胞无法再生的动物身上一再这一历程上面。科学家说,这类研究的某些成就有年夜概开始应用在人类身上。一条令人鼓动的动静是,鲁贝尔已经和华盛顿年夜学另一名科学家年夜卫?雷布尔(David Raible)一路相助辨认出了能够掩护毛细胞不受侵害的化学物质。在他们的尝试中,斑马鱼身上活的毛细胞被染色。然后,研究职员在一个盘子上的96个浅孔中放上一至两条斑马鱼──尝试室使用的小斑马鱼仅有1/8英寸长。年夜概会对毛细胞起到掩护浸染的差此外化学物质被施用于每一个浅孔中。

    末了,他们再向浅孔中插手一种能够杀作古鱼类毛细胞的化学物质。在显微镜下,研究职员细心不雅察看,探求染液颜色依然鲜亮的斑马鱼,由于这标识表记标帜着它们的毛细胞还活着,意味着起掩护浸染的化学物质看上去完成了它的义务。

    研究职员今朝还在老鼠身上试验那些对鱼类毛细胞有掩护浸染的化学物质。科学家们以为,一旦一种药物被发明可以有效掩护毛细胞,而且使用起来对人类是安适的,这种药物就可以用来辅佐掩护病人们的听力──他们接管的药物治疗,如化疗药物,能将毛细胞杀作古。

    鲁贝尔和雷布尔的团队也在研究斑马鱼的遗传基因,以辨认对毛细胞有掩护浸染的基因符号。

    去年,他们的尝试室相助辨认出了几个似乎可以掩护毛细胞的突变基因和类药殽杂物。他们的科研成就揭晓在《科学平易近众藏书楼──遗传学》(PLoS Genetics)杂志上。在2007年揭晓在《听力研究》(Hearing Research)上的另一项研究中,他们确认了几种对毛细胞有掩护浸染且已被美国食物和药物打点局核准用作其他用途的药物。不过,今朝为止还没有对人体举办过试验。

    他们的团队同时还在举办另一组研究,试图相识导致斑马鱼、鸟类和老鼠的毛细胞再生的基因和其他分子。

    毛细胞四周的细胞被称为"撑持细胞",它们可以转化成毛细胞可能孕育产生新的毛细胞。鲁贝尔的尝试室正在研究这两个进程。"要是我们理解理睬了这种细胞的基因模板,那么我们就可以操作这个模板在哺乳动物身上模拟毛细胞再生,"他说。

    有一项研究发了然一种似乎可以让动物毛细胞再生的发育蛋白。在研究中,一名团队成员发了然小鸡的毛细胞受损后体内一种蛋白质的含量(小鸡的毛细胞可以再生)有所上升。可是,在对老鼠举办的同样的尝试中(老鼠的毛细胞不能再生),该蛋白质的含量没有上升,这意味着该蛋白质年夜概与毛细胞再生有关。

    参预这些尝试的科学家们说,使用药物灌注贯注听力损失踪的临床尝试有年夜概会在十年内实现。可是,找到操作毛细胞再生治疗听力损失踪的步伐年夜概还必要至少20年的时刻。

    "助听器是办理题目的一个权宜之计,"美国耳聋和其他雷同窒碍研究所(National Institute on Deafness and Other Communication Disorders)听力损失踪再生和成长项目的认真人南希?弗里曼(Nancy Freeman)暗示。

    "操作这种(促进毛细胞再生的)要领,我们但愿有朝一日可以找到一种要领让听力能够自然地获得规复。"




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