Episode Transcript
Interviewer: Research that gives us a new understanding of common yet relatively unknown birth defect, congenital diaphragmatic hernia.
Examining the latest research and telling you about the latest breakthroughs, The Science and Research show is on The Scope.
I'm talking with Dr. Gabrielle Kardon, Associate Professor in Human Genetics at the University of Utah. 她刚刚在《大发体育官网》杂志上发表了一项研究，为大发娱乐大发娱乐提供了先天性膈疝（CDH）病因的新视角. Dr. Kardon, I had not heard of CDH before can explain what that is?
Dr. Kardon: Most people are familiar with hernias as inguinal hernias and so in an inguinal hernia, 你的腹壁有一个弱点，你的内脏基本上是从腹部伸出来的. And what you can think of CDH as an inguinal hernia in reverse. 所以你的内脏不是往下而是向上穿过脆弱的横膈膜然后向上进入胸腔最大的问题是如果你的肝脏和内脏进入胸腔, they will basically interfere with the growth of the lungs.
Interviewer: Before your research what did we know about how this birth defect happens?
Dr. Kardon: So I would say the majority of the information about CDH actually comes from human geneticist. 他们从CDH患者身上取血样，观察他们的基因，观察他们的基因中是否有突变或者他们的染色体区域是否被删除. 所以基本上大发娱乐知道的是很多基因和一些染色体区域都与CDH的发生密切相关. And the real problem has been that we have no idea how these mutations lead to CDH. And I think that's the problem that we were interested in addressing. How do we go from a mutation to developing a weakness in the diaphragm?
Interviewer: 这就是为什么你的研究如此有见地的部分原因，因为你的研究方法与以前的研究方法完全不同?
Dr. Kardon: Right. 所以大发娱乐刚开始研究横膈膜是如何正常形成的基本上大发娱乐观察了很多不同种类的老鼠大发娱乐可以从基因上标记发育胚胎的不同成分来追踪肌肉细胞的来源, where does the connective tissue come from, where does the tendon come from and how they get linked up.
Interviewer: 这也是你们研究的一部分理解正常情况下会发生什么然后理解CDH的情况下会发生什么.
Dr. Kardon: Right.
Interviewer: So what do we know now about what happens normally and then what goes wrong?
Dr. Kardon: 基本上你可以把横膈膜想象成一圈肌肉细胞，在这个环的中心肌肉细胞与肌腱相连，围绕着每一个肌肉细胞的是一堆结缔组织或胶原蛋白. And that collagen is linking the muscle to the tendon and also the muscle to the bone.
所以通常大发娱乐认为结缔组织基本上是大发娱乐提供结构支持并将物体连接在一起, but basically playing a pretty passive role. 大发娱乐在发育过程中发现的令人惊讶的事情是结缔组织是横膈膜发育的驱动力. It basically told all the other cells what to do.
所以大发娱乐基本上从人类遗传学研究中得到了启示大发娱乐基本上研究了一个最重要的基因它被确定为在CDH中起作用这个基因被称为GATA4. 大发娱乐使用了一些奇特的技巧来敲除GATA4及其在特定细胞中的功能.
大发娱乐发现真正令人惊讶的是GATA4在结缔组织中是必不可少的. 现在，当你在结缔组织中去掉GATA4，你就会得到疝气，疝气看起来就像病人的疝气. And so we had weaknesses in the diaphragm. 大发娱乐让肝脏通过横膈膜突出老鼠的肺很小就像人类病人一样大多数老鼠在出生时就死了.
Interviewer: 有一件事让我很惊讶每次你做那个实验都会有这些疝气, which doesn't happen very often in science.
Dr. Kardon: Right. 大发娱乐现在已经观察了数百只这样的老鼠，每次大发娱乐敲除结缔组织中的基因，我应该指出，不是在肌肉中. So in the connective tissue we have these hernias.
Interviewer: The way these hernias develop is actually little bit counterintuitive.
Dr. Kardon: Right, so there's just decades of data on hernias in patients and from that data, 医生们一直认为疝气是横膈膜上的洞，通过这些洞, the liver and the guts can herniate through. And what we found is that in the mice, where we can observe the formation of hernias from the very beginning, what we found is that there hernias are not initially holes in fact what they are, are regions of connective tissue but that have no muscle in them. And so they are not actually holes.
所以这些洞可能会在之后形成，因为肝脏一直突出这个区域，这个区域很弱，没有肌肉，但最初它并不是一个洞. 这与内科医生和儿科外科医生的教条完全相反.
Interviewer: Now that you have all this basic information what can you do with that?
Dr. Kardon: 所以大发娱乐知道结缔组织是问题所在另一件令人惊讶的事情是这个缺陷很早就出现了. 所以一般来说，在人类中，母亲在大约20周的时候通过超声波得知她的孩子患有CDH. And this is quite late and in the mice, where they have a much shorter gestation time, 大发娱乐在怀孕的三分之二的时候会看到疝但是当大发娱乐看得更早的时候大发娱乐会发现缺陷很大, much, much earlier. 事实上，这种缺陷大约相当于人类在子宫内的40到60天，所以要早得多.
但大发娱乐的想法是，大发娱乐可以在大发娱乐的老鼠胚胎中测试一些潜在的治疗方法，看看大发娱乐是否能拯救这些老鼠, that we know will get hernias if we allow them to develop. And can we somehow intervene? 所以很明显，临床试验是很重要的尤其是当你在子宫里做一些潜在的事情的时候. So you need to be able to try to test things in something other than a human. 诀窍在于大发娱乐从来没有一个非常好的小鼠CDH模型，所以我认为这是一个很好的起点，大发娱乐以前从未有过.
Interviewer: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences Radio.