生物与医学2025science.org
氟西汀促进代谢防御以保护免受脓毒症致死
Fluoxetine promotes metabolic defenses to protect from sepsis-induced lethality
专业 · 约 60 分钟读完前置知识：脓毒症病理生理学基础、药理学基础、代谢与免疫交叉知识
导读
这篇发表在 Science Advances 的研究报告，常用抗抑郁药氟西汀（百忧解，一种 SSRI）能够增强机体的代谢防御，从而在脓毒症中降低致死率、提供保护。标题强调的是一种已有药物被重新用于对抗脓毒症的可能性，具体机制细节未在标题中说明。
HN 关注点：HN 读者一方面对脓毒症致死之快、急诊误判有切身之痛，另一方面质疑把作用广泛、副作用众多的 SSRI 当作脓毒症防治手段是否现实。
HN 评论精选
这几条评论里：质疑 2 补充 1 亲历 1
质疑从药理学角度批评 SSRI 选择性差、副作用多，认为把它作为脓毒症预防手段极不现实。
刚进住院医培训时，我的主治医生曾这样形容所有作用于再摄取的药物（无论拮抗、激动还是双向模型）：这就像发现汽车机油不够，于是往发动机缸体外面浇上几十升机油。一部分确实到了该去的地方，其余则在外部和不该有油的地方把发动机糊住。几乎所有作用于 5-HT 的药物（氟西汀作用于 2C）同时也会作用于其他受体。氟西汀还作用于 α1、M1-4 等许多受体，选择性很差，名副其实是一大桶机油。它也正因此导致长 QT 间期、进食障碍、腹泻、妊娠期缩短、口干、性功能障碍等。当然，泼下这么一桶油也可能通过炎症通路激活 IL-10，更重要的是对抗高甘油三酯血症。但这不该被当作解决方案来推销。再打个牵强的比方：如果我在后备箱里装满 C4 炸药，车子的某些部件肯定能超过标称最高时速，但那不是我们想要的结果。作为最后一搏我会考虑它，但像文中暗示的那样“预防性”使用，那就太牵强了。
medimikka查看英文原文
When I went into residency, my attending once described any drug acting on reuptake (be it antagonistically, agonistic, or in a bifurcated model) as the medical equivalency of noticing your car is low on oil and, in response, pouring a few dozen liters of the stuff over the engine block. Some gets to where it needs to be, the rest gunks up the engine on the outside and in places it shouldn't be. Almost any drug acting on 5HT (fk acts on 2C), acts on other receptors as well. Fk acts on α1, M1-4, and many more, it's not very selective. A venerable bucket of oil, indeed. This is, what also causes Long-QT, feeding disorders, diarrhea, shorter pregnancies, dry mouth, sexual dysfunction, and more. Sure, dropping such a bucket of oil can also, via inflammatory pathways, elicit IL-10 activation and, more importantly, act against hypertriglyceridemia. But that should not be sold as a solution to a problem. Again, to stay with contrived comparisons, if I load the boot of a car with C4, I am sure that some parts of the car will reach more than the car's stated maximum speed. But that's not a desirabe outcome. As a last ditch, I'd consider it. But "preventatively" as suggested... that's a far, far, reach.
亲历亲历朋友因脓毒症被急诊误判延误而死亡，期盼研究能带来急救疗法。
这篇文章来得正是时候——我昨天刚参加完一位非常亲密朋友的葬礼，他就是死于脓毒症。急诊当时告诉他，回家休息就好，腹痛大概是结肠炎发作。我想知道基于这项研究，将来是否会出现针对脓毒症的“抢救性疗法”。希望如此。
jasongill查看英文原文
This article is timely - I just returned home yesterday from the funeral of a very close friend who died of sepsis. He was told at the ER that he just needed to go home and rest and that his stomach pain was likely a colitis flare-up. I wonder if there will ever be a "rescue treatment" for sepsis that is based on this research. Lets hope so.
质疑质疑研究的实用价值，认为不太可能真的用抗抑郁药防治脓毒症。
我的疑问是，为什么要把时间和经费花在这项研究上，而不是研究它对大脑的长期影响，或者停药后会发生什么。这个发现固然有趣，也许能成为精神科医生的一段说辞，但这研究有什么实际用处？我当然不希望有脓毒症风险的人被开抗抑郁药来治疗它，也不希望已经在服药的人因此就不开抗生素。即便作为脓毒症的辅助治疗，我也高度怀疑其可行性。或许这项研究能为未来药物设计提供机制上的启发，但即便这个理由也显得牵强。
willy_k查看英文原文
My question is why is time and money being spend on researching this, as opposed to something like its long term effects on the brain or what happens when it’s use stopped. Sure this finding is a fun thing that might be lumped into a psychiatrist’s spiel, but is there any utility for this research? I certainly hope that someone at risk for sepsis wouldn’t be prescribed an antidepressant to treat it, or that someone already on it wouldn’t be prescribed an antibiotic anyway. Even as an adjunct for sepsis I would be highly skeptical of its practicality. Perhaps the research may provide insights into mechanisms that future drugs may be designed to exploit, but even that seems like a stretch as a justification.
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