经济学人27:关节炎与肉毒杆菌毒素

 　　Science and Technolgy

　　科技

　　Arthritis¹ and botulinum toxin²

　　关节炎与肉毒杆菌毒素

　　Something to celebrate

　　值得庆贺

　　Botulinum toxin may help relieve chronic³ pain

　　肉毒杆菌毒素也许能够帮助缓解慢性疾病的痛苦

　　ARTHRITIS is the bane of millions of lives. Though it comes in many forms, their common theme is inflammation of the tissues around a joint⁴ in the skeleton. Treatment is merely palliative: anti-inflammatory drugs, painkillers⁵ or both. But a piece of research published this week in Biochemistry, by Edwin Chapman of the University of Wisconsin and his colleagues, offers arthritis sufferers hope from a strange quarter: botulinum toxin.

　　关节炎是数百万人的噩梦。关节炎有多种形式，但它们共同的特征是关节处组织的炎症反应。对此的治疗手段往往是治标不治本：消炎药，止痛药，或者两者同时用。但是由威斯康辛大学埃德文?查普曼博士以及他的同事们在本周生物化学杂志上的发表的一项研究，为关节炎患者提供了希望：肉毒杆菌毒素。

　　This toxin is one of the most dangerous substances on earth. It is made by a bacterium⁶ called Clostridium botulinum. Even a small amount (less than a microgram) is enough to kill a healthy adult. The toxin molecules⁸ attach themselves to a protein called synaptotagmin, which is found on the surface membranes⁹ of nerve cells at their junctions¹⁰ with muscle cells. Thence they are ingested into the cell, where they disable another protein, SNAP-25, the role of which is to help release a chemical messenger called acetylcholine. This messenger's job is to tell muscle cells to contract. Without that signal, muscles stops working. If this happens all over the body, death is rapid.

　　这种毒素是地球上最危险的物质之一，它是由一种叫肉毒杆菌的细菌合成。仅仅很小的量（小于一微克）就足以杀死一个健康成年人。这种毒素能结合到一种叫做synaptotagmin（SYT）的蛋白上，SYT则位于神经肌肉接头处神经细胞的细胞膜表面。然后这种毒素被吞入细胞内部，进而让另外一个叫SNAP-25的蛋白失活，SNAP-25的作用是帮助一种叫乙酰胆碱的化学信使的释放。这种化学信使的作用则是让肌肉细胞进行收缩。没有这种信号的话，肌肉便停止工作了。如果全身都发生这样的情况，死亡便接踵而来。

　　Inject the toxin locally, though, and you can do some good. It wipes away frown lines and other wrinkles, which are caused by overstimulated muscles, thus allowing ageing celebs to appear on the covers of gossip magazines without embarrassment¹¹. More seriously, it is used to treat disorders¹² ranging from headaches to muscle spasms¹³. It only works, however, in cells that have synaptotagmin on their surfaces. Which is where Dr Chapman comes in.

　　然而局部注射肉毒素还能带来好处。它能抚平额头和其他部位的皱纹，这些皱纹恰恰是因为肌肉被过度刺激引起的。它使得那些上了年纪的名流们毫无尴尬的出现在街头杂志的封面。它更为严肃的用途是治疗各种生理紊乱，包括从头痛到肌肉痉挛。然而，它仅仅能在那些表面具有SYT蛋白的细胞中起作用，这正是查普曼博士的切入点。

　　Inflammation is also caused by chemical signalling. Cells called macrophages summon all sorts of others to an injury, to try to repair it. If repair cannot be effected, though (as is the case in arthritis), the signalling never stops. The swelling¹⁴ causes pain, and the patient suffers. But macrophage signalling also involves SNAP-25, so Dr Chapman thinks he can use botulinum toxin to shut the cells up.

　　炎症反应同样是由化学信号引起的。巨噬细胞召集其他免疫细胞到达受伤处，并试图修复伤害。但如果修复不起作用（如同关节炎的情况），则这些信号就不会停止。肿痛造成痛苦，而病人只能忍受。但是巨噬细胞的信号通路中也包括SNAP-25，因此查普曼博士想，他能够用肉毒素来关闭这些免疫细胞。

　　The problem is that macrophages have no synaptotagmin on their surfaces. They do, though, have other proteins, called Fc receptors. What is needed is a way to get toxin molecules to attach themselves to Fc receptors. And this is what Dr Chapman thinks he has managed. His trick is to link each molecule⁷ to an antibody. An antibody is a protein that binds¹⁵ to a hostile invading organism. If this does not kill the invader¹⁶ outright¹⁷, then it acts as a flag for the bug¹⁸ in question to be eaten by a macrophage. That happens when the antibody that is attached to the invader also attaches itself to an Fc-receptor molecule. This done, the invader is ingested.

　　问题在于，巨噬细胞的表面并没有SYT蛋白，他们表面有的是另外一种被称为Fc受体的蛋白。现在只需要找到一个办法，让肉毒素结合到Fc受体上去，而查普曼博士认为，他办到了这一点。他的绝招是将每个分子与抗体连接起来。抗体是一种能结合入侵有机体的分子，如果抗体不能马上杀死入侵者，则它将作为入侵者的一个标记，使得它们有可能被巨噬细胞所吞噬，这个过程只有当结合在入侵者上的抗体同时也能和Fc受体分子结合时才会发生，而这个步骤一完成，则入侵者就被吞噬了。

　　Dr Chapman's plan was to use this mechanism¹⁹ to get macrophages to eat toxin molecules. Once inside, they would disable SNAP-25 and thus stop the release of signalling molecules in the way they do in nerve cells. The result, the theory goes, would be an end to the chronic inflammation that arthritis causes, and thus to the chronic pain.

　　查普曼博士的计划是，利用这个机制，让巨噬细胞把肉毒素吞进去，而进入细胞之后，它就能使SNAP-25失去活性，从而像在神经细胞中一样，阻止信号分子的释放。如果这个理论可行，那么由关节炎所导致的慢性炎症将被终结，同时被终结的，还有长期以来的痛苦。

　　The first stage works. The toxin/antibody complex successfully gloms onto the macrophages. The toxin does get inside them. And the cells do stop signalling. It is a long way from there to a treatment, but Dr Chapman has made the trick work in mice as well as Petri dishes (injecting the complex does, indeed, stop macrophages recruiting). Many more animal trials will be needed before it can be tested on people. But for those who suffer the chronic pain of arthritis, it is a hopeful start.

　　第一步看起来是可行的。肉毒素与抗体的复合物成功地黏附上巨噬细胞，肉毒素确实进入了巨噬细胞内部，这些细胞也的确中止了信号通路。从这一步到治疗仍有很长的路要走，但是查普曼博士已经用这个方法在培养皿的细胞中和在老鼠身上获得了成功（注入这种复合物确实阻止了巨噬细胞的招募）。在人体上进行测试前，还需要完成更多的动物实验，但是对于那些正在长期忍受关节炎痛苦的人们来说，这是一个充满希望的开始。

1 arthritis   

n.关节炎

参考例句：

• Rheumatoid arthritis has also been linked with the virus.风湿性关节炎也与这种病毒有关。
• He spent three months in the hospital with acute rheumatic arthritis.他患急性风湿性关节炎，在医院住了三个月。

2 toxin   

n.毒素，毒质

参考例句：

• Experts have linked this condition to a build-up of toxins in the body.专家已把这一病症与体内毒素的积累联系起来。
• Tests showed increased levels of toxin in shellfish.检验表明水生有壳动物的毒素水平提高了。

3 chronic   

adj.(疾病)长期未愈的，慢性的；极坏的

参考例句：

• Famine differs from chronic malnutrition.饥荒不同于慢性营养不良。
• Chronic poisoning may lead to death from inanition.慢性中毒也可能由虚弱导致死亡。

4 joint   

adj.联合的，共同的；n.关节，接合处；v.连接，贴合

参考例句：

• I had a bad fall,which put my shoulder out of joint.我重重地摔了一跤，肩膀脫臼了。
• We wrote a letter in joint names.我们联名写了封信。

5 painkillers   

n.止痛药( painkiller的名词复数 )

参考例句：

• The doctor gave him some painkillers to ease the pain. 医生给了他一些止疼片以减缓疼痛。 来自辞典例句
• The primary painkillers - opiates, like OxyContin - are widely feared, misunderstood and underused. 人们对主要的镇痛药——如鸦片剂奥施康定——存在广泛的恐惧、误解，因此没有充分利用。 来自时文部分

6 bacterium   

n.(pl.)bacteria 细菌

参考例句：

• The bacterium possibly goes in the human body by the mouth.细菌可能通过口进入人体。
• A bacterium is identified as the cause for his duodenal ulcer.一种细菌被断定为造成他十二指肠溃疡的根源。

7 molecule   

n.分子，克分子

参考例句：

• A molecule of water is made up of two atoms of hygrogen and one atom of oxygen.一个水分子是由P妈̬f婘̬ 妈̬成的。
• This gives us the structural formula of the molecule.这种方式给出了分子的结构式。

8 molecules   

分子( molecule的名词复数 )

参考例句：

• The structure of molecules can be seen under an electron microscope. 分子的结构可在电子显微镜下观察到。
• Inside the reactor the large molecules are cracked into smaller molecules. 在反应堆里，大分子裂变为小分子。

9 membranes   

n.（动物或植物体内的）薄膜( membrane的名词复数 )；隔膜；（可起防水、防风等作用的）膜状物

参考例句：

• The waste material is placed in cells with permeable membranes. 废液置于有渗透膜的槽中。 来自辞典例句
• The sarcoplasmic reticulum is a system of intracellular membranes. 肌浆网属于细胞内膜系统。 来自辞典例句

10 junctions   

联结点( junction的名词复数 )； 会合点； （公路或铁路的）交叉路口； （电缆等的）主结点

参考例句：

• Metals which were mutually soluble would tend to give strong junctions. 可互溶的金属趋向于产生牢固的结合点。
• Some adhering junctions are present as narrow bands connecting two cells. 有些粘附连接以一窄带的形式连接两个细胞。

11 embarrassment   

n.尴尬；使人为难的人(事物)；障碍；窘迫

参考例句：

• She could have died away with embarrassment.她窘迫得要死。
• Coughing at a concert can be a real embarrassment.在音乐会上咳嗽真会使人难堪。

12 disorders   

n.混乱( disorder的名词复数 )；凌乱；骚乱；（身心、机能）失调

参考例句：

• Reports of anorexia and other eating disorders are on the increase. 据报告，厌食症和其他饮食方面的功能紊乱发生率正在不断增长。 来自《简明英汉词典》
• The announcement led to violent civil disorders. 这项宣布引起剧烈的骚乱。 来自《简明英汉词典》

13 spasms   

n.痉挛( spasm的名词复数 )；抽搐；（能量、行为等的）突发；发作

参考例句：

• After the patient received acupuncture treatment,his spasms eased off somewhat. 病人接受针刺治疗后，痉挛稍微减轻了。 来自《简明英汉词典》
• The smile died, squeezed out by spasms of anticipation and anxiety. 一阵阵预测和焦虑把她脸上的微笑挤掉了。 来自辞典例句

14 swelling   

n.肿胀

参考例句：

• Use ice to reduce the swelling. 用冰敷消肿。
• There is a marked swelling of the lymph nodes. 淋巴结处有明显的肿块。

15 binds   

v.约束( bind的第三人称单数 )；装订；捆绑；（用长布条）缠绕

参考例句：

• Frost binds the soil. 霜使土壤凝结。 来自《简明英汉词典》
• Stones and cement binds strongly. 石头和水泥凝固得很牢。 来自《简明英汉词典》

16 invader   

n.侵略者，侵犯者，入侵者

参考例句：

• They suffered a lot under the invader's heel.在侵略者的铁蹄下，他们受尽了奴役。
• A country must have the will to repel any invader.一个国家得有决心击退任何入侵者。

17 outright   

adv.坦率地；彻底地；立即；adj.无疑的；彻底的

参考例句：

• If you have a complaint you should tell me outright.如果你有不满意的事，你应该直率地对我说。
• You should persuade her to marry you outright.你应该彻底劝服她嫁给你。

18 bug   

n.虫子；故障；窃听器；vt.纠缠；装窃听器

参考例句：

• There is a bug in the system.系统出了故障。
• The bird caught a bug on the fly.那鸟在飞行中捉住了一只昆虫。

19 mechanism   

n.机械装置；机构，结构

参考例句：

• The bones and muscles are parts of the mechanism of the body.骨骼和肌肉是人体的组成部件。
• The mechanism of the machine is very complicated.这台机器的结构是非常复杂的。