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修复肝脏瘢痕的新疗法 – 译学馆
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修复肝脏瘢痕的新疗法

Scar wars: Repairing the liver

肝纤维化曾被认为是不可逆转的
Scarring of the liver was once thought to be an irreversible situation,
但一项令人激动的药物试验
but a new and exciting field of experimental drugs
或许有望给这种传统看法划上句号
may put an end to this dogma.
抗击瘢痕
肝脏是一个大大的外表光滑的器官
The liver is a large smooth organ
它承担着人体的多种基本功能
that carries out many essential functions.
肝脏可以储存并释放营养物质
It stores and releases nutrients,
帮助消化 并分解多余物质
aids digestion and breaks down unwanted substances.
不幸的是 许多慢性疾病会损伤肝脏
Unfortunately, numerous chronic diseases damage the liver
长期损伤会导致瘢痕的产生
and when they continue for a long time they cause scarring
这种症状被称为“肝硬化”
— a condition called fibrosis.
引发肝硬化最常见的原因有:肝炎病毒 长期酗酒
The most common causes arehepatitis viruses, long-term heavy drinking
由肥胖和糖尿病引发的脂肪肝疾病
and fatty liver disease associatedwith obesity and diabetes.
瘢痕是由纤维状的胶原蛋白聚集造成的
This scarring is caused by a buildup of fibrous collagen proteins
这些胶原蛋白会逐渐取代健康的组织
which begin to replace healthy tissue.
如果纤维化持续恶化
If the fibrosis keeps worsening,
就会发展成肝硬化
the liver can progress to a state known as cirrhosis
在这个阶段
At this stage,
过多的瘢痕阻碍了肝脏的血流运行
excessive scarring hampers the liver’s blood flow
使其无法正常工作
and stops it being able to do its job.
没有及时治疗的肝硬化会直接导致肝衰竭
Unchecked cirrhosis can lead directly to liver failure,
进而高度增加患上肝癌的风险
and puts patients at high risk for liver cancer.
全球每年有100万人因肝硬化失去生命
Cirrhosis currently kills a million people worldwide each year.
好消息是 肝脏自身有一套消除瘢痕组织的机制
The good news is that the liver has its own mechanisms that degrade scar tissue,
这个发现掀起了新一轮药物研发浪潮
and this discovery has spurred a new wave of research
研究人员希望开发出
into developing drugs
可以阻止纤维化进一步发展的药物
which can halt the progression of fibrosis,
或是在基础疾病得到治愈后加速瘢痕愈合的药物
or speed up healing once the underlying disease has been treated.
减少纤维化的做法是避免所有诱因
The best way to reduce fibrosis is to avoid it altogether
消除与疾病相关的风险因素
by removing the risk factors associated with the disease,
但如今 科学家正在研究形成瘢痕的细胞的生物学机制
but now scientists are examining the biology of the scar-causing cells
把它们作为干预治疗的潜在靶点
as potential targets for therapeutic interventions
瘢痕是由肌成纤维细胞产生的
Scars are generated by cells called myofibroblasts.
这些细胞一旦被激活
When these cells become activated,
就会增殖 并移动到肝部损伤的区域
they proliferate, migrate to injury sites
向细胞外基质分泌胶原
and secrete collagen into the extracellular matrix.
随着这些胶原纤维的不断积累
As these collagen fibres accumulate,
它们会交叉成网状
they become cross-linked into a mesh
使组织变硬 阻断其正常工作
which stiffens the tissue and blocks its function.
因此 研究人员将肌成纤维细胞作为首要的靶向目标
So researchers are aiming their sites, first and foremost, at myofibroblasts.
一种方法是靶向调控激活肌成纤维细胞的信使分子
One strategy is to target the messenger molecules which coordinate their activation.
受损的肝脏细胞和免疫细胞会释放这些信使分子
These are released by damaged liver cells and immune cells
药物研发可以将这些信使分子作为靶标
and could targeted by new drugs.
一种名为Cenicriviroc的药物
One example is a drug called Cenicriviroc
可以阻断这些促纤维化信使的受体
that blocks receptors for profibrosis
这些受体被称为细胞因子
messengers called cytokines.
另一类药物通过靶向肌成纤维细胞表面的整合素使其失活
Another set of drugs could inactivate myofibroblasts by targeting receptors on their surface called integrins
整合素能让肌成纤维细胞
that allow them to interact with other cells
与其它细胞和细胞外基质相互作用
and the extracellular matrix.
一系列类似作用机制的药物正在研发中
Multiple drugs that work this way are currently being explored
并且很快就会开始进行人体试验
and will enter human trials soon.
另一种选择是阻断肌成纤维细胞制造胶原的能力
Blocking the myofibroblasts’ ability to make collagen is another option.
这些药物通过将少量RNA插入肌成纤维细胞核
These drugs work by inserting small bits of RNA into the nucleus of myofibroblasts,
破坏其制造胶原纤维的机制
destabilising the machinery that creates collagen fibres.
还有一种方法是阻断让胶原纤维交叉连接的酶
Another approach is to block the enzymes that cross-link collagen fibres
使其无法让瘢痕基质硬化
to stiffen the scar matrix.
这会让胶原更容易被人体降解
This makes the collagen easier for the body to degrade.
最后一个令人兴奋的新方法是细胞疗法
Finally, an exciting new avenue is the use of cell therapies.
向小鼠肝脏注入额外的巨噬细胞
Introducing extra immune cells called macrophages into rodents’ livers
可以极大地增强肝脏本身的瘢痕消除机制
strongly boosts the organ’s intrinsic anti-scarring mechanisms
使用患者自身巨噬细胞的人体试验也已经开始了
and now human trials using patient’s own macrophages have begun.
所有这些疗法都需要进行临床试验
All these therapies will require clinical trials,
而由于肝纤维化进展缓慢
and due to the slow progressive nature of liver fibrosis,
这些试验可能需要数年之久
this may take years.
但研发过程中出现的新型生物标志物
But new biomarkers in development
有望大幅加速试验进程
may speed up trials considerably
它们能在整体纤维化水平下降前
by showing whether the drugs are working,
就指示药物是否有效
even before the overall fibrosis starts to decline.
希望这些新方法能帮助我们取得瘢痕大战的胜利
Hopefully these new approaches will help us to victory in the scar wars.

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视频概述

由许多原因引发的肝脏瘢痕曾被认为是不可治愈的,而肝脏瘢痕进一步发展就会导致肝纤维化,进而引发肝硬化。现在随着研究的逐渐进展,肝脏瘢痕有望得到消除,科学家是如何做到的呢?

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https://www.youtube.com/watch?v=a0d1yvGcfzQ

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