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热休克蛋白在急性肺损伤中:治疗的死胡同(?)

HS in acute lung injury: a therapeutic dead end(?).

作者信息

Merz Tamara, Denoix Nicole, Wepler Martin, Gäßler Holger, Messerer David A C, Hartmann Clair, Datzmann Thomas, Radermacher Peter, McCook Oscar

机构信息

Institute for Anesthesiological Pathophysiology and Process Engineering, Ulm University Medical Center, Helmholzstraße 8/1, 89081, Ulm, Germany.

Clinic for Psychosomatic Medicine and Psychotherapy, Ulm University Medical Center, Ulm, Germany.

出版信息

Intensive Care Med Exp. 2020 Dec 18;8(Suppl 1):33. doi: 10.1186/s40635-020-00324-0.

Abstract

This review addresses the plausibility of hydrogen sulfide (HS) therapy for acute lung injury (ALI) and circulatory shock, by contrasting the promising preclinical results to the present clinical reality. The review discusses how the narrow therapeutic window and width, and potentially toxic effects, the route, dosing, and timing of administration all have to be balanced out very carefully. The development of standardized methods to determine in vitro and in vivo HS concentrations, and the pharmacokinetics and pharmacodynamics of HS-releasing compounds is a necessity to facilitate the safety of HS-based therapies. We suggest the potential of exploiting already clinically approved compounds, which are known or unknown HS donors, as a surrogate strategy.

摘要

本综述通过对比临床前研究的 promising 结果与当前临床实际情况,探讨了硫化氢(HS)疗法用于急性肺损伤(ALI)和循环性休克的合理性。该综述讨论了狭窄的治疗窗和宽度、潜在的毒性作用、给药途径、剂量和时间安排都必须非常谨慎地权衡。开发用于测定体外和体内 HS 浓度以及 HS 释放化合物的药代动力学和药效学的标准化方法,对于促进基于 HS 的疗法的安全性而言是必要的。我们建议将已获临床批准、已知或未知为 HS 供体的化合物作为替代策略加以利用的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3391/7746532/bf2a3ab1a9c2/40635_2020_324_Fig1_HTML.jpg

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