筛查药物不良反应有新招

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New test shows source of disease side-effects
WASHINGTON (Reuters) - A new panel of tests aimed at finding out how drugs may damage cells has turned up a series of interactions that may explain some of the serious side-effects of statin drugs, researchers said on Sunday.
华盛顿（路透社）报道，一系列本来旨在研究药物损伤细胞的机制的实验，后来却意外发现了他汀类导致一些严重不良反应的原因。
Statins, the wildly popular cholesterol-lowering drugs, may interact with at least one blood pressure drug to damage the mitochondria, the powerhouses of cells, the researchers reported in the journal Nature Biotechnology.
《Nature Biotechnology》报道，他汀类作为一种广泛应用的降脂药，会和至少一种降压药互相作用进而损害细胞的能量来源线粒体。
Their study also may lead to the development of drugs to treat diabetes and diseases of aging and better ways to screen for drug side-effects, the researchers said.
这项研究还可能引导开发治疗糖尿病和一些退化性疾病的药物，也会指导筛查药物的不良反应。
Vamsi Mootha of the Broad Institute at Harvard University and the Massachusetts Institute of Technology said they had made their new database freely available to other scientists to use for screening drugs.
来自哈佛和麻省的研究者说，他们已经将该研究的数据公开，让其他的研究者都可以利用该方法进行药物筛查。
The mitochondria are structures in cells that make adenosine triphosphate, or ATP, which helps power cells. Mootha's team tested more than 2,000 drugs on cells to see how they might interfere with this process.
线粒体是细胞内生产三磷酸腺苷即ATP的结构，能够给细胞活动提供能量。研究小组一共测试了2000多种药物，来观察它们对线粒体产生能量的影响。
Their test looks at gene function, ATP levels and other measures of how well the mitochondria are working.

他们评判的标准是基因功能、ATP水平及其他一些代表线粒体功能的指标。

Many patients who take statins have reported side-effects that include muscle pain and weakness. The cause is not well understood but Mootha has long suspected the mitochondria are involved. The effects have been hard to pin down because studies of different groups have produced conflicting results.

很多使用他汀类药物的患者会出现一些副作用，包括肌肉疼痛和疲乏感。具体的机制一直未能明了，但是研究者考虑是与线粒体有关的。但是由于不同的研究小组总是得出矛盾的结论，所以一直没有确定。

Mootha's team said their findings showed some statins lower ATP levels and interfere with the mitochondria.

而该研究发现，一些他汀类药物是能降低ATP水平的，并会与线粒体互相作用的。

Fluvastatin is sold by Novartis under the brand name Lescol, lovastatin is sold under the brand name Mevacor and simvaststin is sold as Zocor.

包括诺华的氟伐他汀钠（来适可）、洛伐他汀（美降脂）及辛伐他汀（舒降之）。

PATTERN OF DYSFUNCTION

功能障碍的类型

Three others -- atorvastatin, made by Pfizer under the brand name Lipitor, pravastatin or Pravachol, made by Bristol Myers Squibb and rosuvastatin, sold under the Crestor brand name by AstraZeneca -- had little effect, they said.

另外三种，包括辉瑞的阿托伐他汀（立普妥）、百时美施贵宝公司的普伐他汀(普拉固）及阿斯利康的罗伐他汀（冠脂妥）的影响不大。

\"We asked what pattern of dysfunction they cause in the mitochondria,\" Mootha said in a telephone interview. \"Once we figured out what the pattern was we asked what other FDA-approved drugs give rise to that same pattern of mitochondrial dysfunction.\"

研究者说，他们研究了这种线粒体损害的类型，一旦他们明确了机制，就会进一步明确还有哪些FDA批准的药物引起了类似的线粒体损害不良反应。

They found a few.

发现很少

\"We were struck by the fact that one of these nearest-neighbor drugs is propranolol, a widely used antihypertensive agent,\" they wrote.

他们发现，与他汀类引起的不良反应最接近的是降压药普萘洛尔，这让他们很惊讶。

Propranolol is a so-called beta blocker drug sold by Wyeth under the brand name Inderal and also available generically.

普萘洛尔由惠氏生产，商品名是 Inderal ，也很是畅销。

\"That was a bit of a surprise,\" Mootha said. \"And it is important because so many patients are on a statin as well as blood pressure medication.\"

这更让人惊讶了，重要的是，很多患者会同时使用他汀类和降压药。

Other drugs that resembled statins in their activity in mitochondria included amoxapine, cyclobenzaprine, griseofulvin, pentamidine, paclitaxel, propafenone, ethaverine, trimeprazine and amitriptyline.

其他一些会和他汀类一样引起线粒体损害的药物包括阿莫沙平、环苯扎林、灰黄霉素、喷他脒、紫杉醇、普罗帕酮、依沙维林、异丁嗪和阿米替林。

A similar process may be going on in diabetes, nerve degeneration and aging, Mootha's team said. They found a number of drugs, including the cancer drug vinblastine may counter this process.

同样的机制发生在糖尿病、神经退行性疾病及衰老过程中；同时，研究团队也发现，一些药物，包括抗癌药vinblastine可能会对抗这个作用。

Mootha cautioned that his group has worked only in batches of muscle cells grown in the lab so far and that far more tests are needed.

但是他们也承认，仅仅只是在一些肌肉细胞上做了实验，还需要更多的实验来验证。