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肽类激素松弛素:从实验室到临床应用

Peptide hormone relaxin: from bench to bedside.

作者信息

Jelinic Maria, Marshall Sarah A, Stewart Dennis, Unemori Elaine, Parry Laura J, Leo Chen Huei

机构信息

School of BioSciences, The University of Melbourne , Parkville, Victoria , Australia.

Molecular Medicine Research Institute , Sunnyvale, California.

出版信息

Am J Physiol Regul Integr Comp Physiol. 2018 Jun 1;314(6):R753-R760. doi: 10.1152/ajpregu.00276.2017. Epub 2018 Feb 7.

Abstract

The peptide hormone relaxin has numerous roles both within and independent of pregnancy and is often thought of as a "pleiotropic hormone." Relaxin targets several tissues throughout the body, and has many functions associated with extracellular matrix remodeling and the vasculature. This review considers the potential therapeutic applications of relaxin in cervical ripening, in vitro fertilization, preeclampsia, acute heart failure, ischemia-reperfusion, and cirrhosis. We first outline the animal models used in preclinical studies to progress relaxin into clinical trials and then discuss the findings from these studies. In many cases, the positive outcomes from preclinical animal studies were not replicated in human clinical trials. Therefore, the focus of this review is to evaluate the various animal models used to develop relaxin as a potential therapeutic and consider the limitations that must be addressed in future studies. These include the use of human relaxin in animals, duration of relaxin treatment, and the appropriateness of the clinical conditions being considered for relaxin therapy.

摘要

肽类激素松弛素在孕期内外均发挥着多种作用,且常被视为一种“多效性激素”。松弛素作用于全身多个组织,具有许多与细胞外基质重塑和脉管系统相关的功能。本文综述探讨了松弛素在宫颈成熟、体外受精、先兆子痫、急性心力衰竭、缺血再灌注以及肝硬化等方面的潜在治疗应用。我们首先概述了临床前研究中用于推动松弛素进入临床试验的动物模型,然后讨论这些研究的结果。在许多情况下,临床前动物研究的积极结果并未在人体临床试验中得到重现。因此,本文综述的重点是评估用于开发松弛素作为潜在治疗药物的各种动物模型,并考虑未来研究中必须解决的局限性。这些局限性包括在动物中使用人松弛素、松弛素治疗的持续时间以及考虑用于松弛素治疗的临床病症的适用性。

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