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这条小鱼正改变着现代医学

The Tiny Fish That's Changing Modern Medicine

当你看一条斑马鱼时 看到的可能只是一条可爱的
When you look at a zebrafish, you probably just see a cute, tiny fish that’s smaller
比小拇指还袖珍的小鱼
than your pinky finger.
但这条小鱼远不止看起来那么简单
But this little fish is so much more than that.
你正看到一件令人惊叹的科学工具 而它已经带来了一些重大发现
You’re looking at an amazing scientific tool that has led to some major discoveries.
自20世纪70年代起 斑马鱼就被用于研究脊椎动物的进化历程
Zebrafish have been used since the 1970s to study the development of vertebrates, and
最近 它们在帮助科学家进一步地了解人类疾病
more recently, they’ve been helping scientists learn more about human diseases and maybe
甚至可能开发出一些具有潜力的疗法
even develop some potential treatments.
那么 科学家为什么选用斑马鱼呢?
So why the zebrafish?
首先 像所有鱼类一样 斑马鱼的基因组与人类相似 这主要因为我们有
Well, like all fish, their genomes are similar to the human genome, mainly because we share
共同的祖先
a common ancestor.
斑马鱼拥有超过26000个蛋白编码基因 其中大约70%
They have over 26,000 protein-coding genes, and about 70% of those genes are related to
与人类基因相对应
similar genes in humans.
由于对斑马鱼的研究已经十分深入 我们了解到大约80%已确定的人体致病基因
Since zebrafish have been studied so much, we know that around 80% of the disease-causing
都至少有一个对应基因存在于斑马鱼体内
genes that have been identified in humans have at least one related gene in zebrafish.
通过研究这些基因在斑马鱼体内的作用 科学家能够更多地了解它们
By studying what these genes do in zebrafish, scientists can learn more about what they
在人体内的作用
do in humans.
其他的原因也促使研究人员专门研究斑马鱼
And there are other reasons researchers specifically study zebrafish:
饲养它们很便宜 且雌鱼在一周内可产下200至300枚卵
They’re cheap to maintain, and the females can spawn around 200 to 300 eggs in a single
这提供了大量的新试验对象
week, which makes for a lot of new test subjects.
更重要的是 斑马鱼的胚胎和幼体都呈透明状 并且生长迅速
More importantly, zebrafish embryos and larvae are transparent and develop really quickly.
甚至有一种转基因的斑马鱼
There’s even a genetically-engineered strain of zebrafish that’s transparent through
终其一生都是透明的
its whole life.
这种透明的特性让研究人员能确切地看见斑马鱼体内发生了什么
That transparency allows researchers to see exactly what’s going on inside the fish’s
并观察生物学过程——比如癌症是怎样形成的
body, and watch biological processes — like how cancers develop.
即便如此 斑马鱼仍然不是人类疾病的完美模型——一方面
That said, zebrafish still aren’t the perfect model for human disease — for one thing,
它们没有肺和乳腺
they don’t have lungs or mammary glands.
另一方面 它们基因组的大部分是由多拷贝基因组成
Plus, a lot of their genome is made up of duplicate genes.
其中一些基因拷贝可能已经突变 获得了祖先基因不具备的功能
Some of those gene copies might have mutated and developed functions that weren’t there
——这使它们不同于人类的版本
in the ancestor’s gene — which would make them different from the human versions.
尽管如此 斑马鱼已经能够帮助科学家了解许多不同的
Even so, zebrafish have been able to help scientists learn about a lot of different
疾病——比如黑素瘤 最危险的皮肤癌类型
diseases — like melanoma, the most dangerous type of skin cancer.
特定基因的突变影响了细胞增殖与凋亡的方式 癌症因此而形成
Cancer develops because of mutations in specific genes that affect how cells multiply and die.
最常见的黑素瘤相关突变叫做BRAF V600E基因突变
And the most common mutation related to the melanoma is called BRAF(V600E).
携带这种突变基因 并且也缺少抑癌基因的斑马鱼成为
Zebrafish that carry this mutation, and also lack a tumor-suppressing gene, make good models
这种疾病的良好模型
for the disease.
因此 研究者可以研究癌症怎样在BRAF基因突变的斑马鱼体内形成 并且用它们
So researchers can study how cancer develops in fish with the BRAF mutation, and use them
来试验治疗方法
to test treatments.
他们也利用斑马鱼来发现其他导致黑素瘤的基因
They’ve also used zebrafish to find other melanoma-causing genes.
要知道 有时BRAF基因突变只会导致良性痣而非黑素瘤
See, sometimes, the BRAF mutation just causes benign moles instead of melanoma.
BRAF基因突变可能会启动这一过程 但另一种基因必须协同工作才能真正导致
BRAF might start the process, but another gene has to cooperate to actually cause the
黑素瘤
melanoma.
问题是怎样才能找到那种基因
The question was how to find that gene.
研究人员使用人类黑素瘤的样本 沿着一条染色体的特定部分寻找可能导致
The researchers used human melanoma samples to look for duplicated genes that might cause
癌症的多拷贝基因
cancer along a certain section of a human chromosome.
他们将找到的多拷贝基因插入到携带
The duplicated genes they found were then inserted into the genomes of zebrafish with
BRAF基因突变的斑马鱼基因组中
the BRAF mutation.
发现只有一种叫做SETDB1的基因 能加速斑马鱼体内黑素瘤的形成
And only one gene, called SETDB1, was found to accelerate melanoma formation in the zebrafish.
这项发现可能推动产生以SETDB1基因为靶点的癌症新疗法
This discovery might lead to the creation of new cancer therapies that target SETDB1.
对斑马鱼的研究也可能会有助于干细胞的移植
Zebrafish research might also be able to help with stem cell transplants.
其原因与一种名为前列腺素E2的复合物有关
And the reason for that has to do with a compound called prostaglandin E2.
在一项研究中 研究人员发现 当使用某些化学物质来增加
In a study, researchers discovered that when certain chemicals were used to enhance prostaglandin
前列腺素E2的合成时 斑马鱼体内造血干细胞的数量上升
E2 synthesis, the amount of hematopoietic, or blood, stem cells in the zebrafish increased.
因此 额外的前列腺素E2可能会有助于治疗正在接受
So, extra prostaglandin E2 might be able to help treat someone who’s getting a blood
造血干细胞移植的人 像白血病患者或是血液或免疫系统紊乱的人
stem cell transplant, like a leukemia patient or someone with a blood or immune system disorder.
这是个非常棒的消息!
Which is great news!
这项发现最终导致了一种名为ProHema的药物的产生 预
This discovery eventually led to the creation of a drug called ProHema that’s supposed
预期它能提高用脐血进行造血干细胞移植的
to improve the success of hematopoietic stem cell transplants using blood from umbilical
成功率
cords.
2014年至2015年 ProHema经历了二期临床试验阶段 即在病人身上试验
Between 2014 and 2015, it went through stage II clinical trials where it was tested on
以观察疗效如何
patients to see how well it works.
测试结果令人倍感希望
And the results are pretty promising.
干细胞移植在服用ProHema的病人体内 似乎要比在控制组更早开始
In patients who were taking ProHema, stem cell transplants seemed to start working earlier
发挥作用
than the control group.
因此 ProHema可能有助于提升干细胞移植的疗效 但它仍需
So, ProHema might help improve the effectiveness of these stem cell transplants, but it still
接受更多的测试
needs to be tested more.
斑马鱼的一个显著特点可能也会在人体组织再生方面帮到科学家
A specific trait of zebrafish might also help scientists with regenerating human tissue.
如果斑马鱼的心脏受损 它能够再生
If a zebrafish heart gets damaged, it can regenerate.
即使部分心脏被移除 也只会在伤口处形成一个凝块 而凝块
Even if part of the heart is removed, it’ll just form a clot at the wound site, which
最终会被新生的心肌取代
eventually gets replaced with new cardiac muscle.
但如果人类心脏的一部分受损–比如由于心脏病–受损的
But if part of a human heart gets damaged — like from a heart attack — the damaged
区域通常只会变成疤痕组织 而疤痕组织的泵血能力弱于健康组织
area generally just turns into scar tissue, which doesn’t pump as well as healthy tissue.
如果能使健康的心肌再生 代替疤痕组织 就可以避免永久性的损伤
If you could regenerate healthy cardiac muscle instead, you could avoid that permanent damage.
虽然仍处于研究中 但似乎斑马鱼能这样而我们不能
While it’s still being studied, it seems like the reason zebrafish can do this and
是因为伤口使它们的心肌细胞活化 而后细胞重新生长
we can’t is because the injury activates their cardiac muscle cells, which then regrow
为组织
the tissue.
随着科学家对该过程的具体研究 人体组织再生的想法
As scientists learn exactly how that’s done, the idea of human tissue regeneration might
距成为现实可能又近了一步
get closer to becoming a reality.
所以 斑马鱼也许很小
So the zebrafish may be tiny.
但它正极大地帮助着现代医学
But it’s helping modern medicine in a big way.
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这一期的话题
Patreon.
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If you want to help support this show, just go to patreon.com/scishow.
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视频概述

斑马鱼虽小,却在现代医学研究中发挥着重要的作用。本期科学秀带你走近神奇的斑马鱼,看看它是怎样改变着现代医学。

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【MR】拾月

视频来源

https://www.youtube.com/watch?v=razup6Xr0JA

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