Zhang Meng Qi, Macala Kimberly F, Fox-Robichaud Alison, Mendelson Asher A, Lalu Manoj M
Clinical Epidemiology Program, Blueprint Translational Group, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada K1H 8M5.
Shock. 2021 Aug 1;56(2):178-187. doi: 10.1097/SHK.0000000000001717.
In this mini-review we provide an overview of sex- and gender-dependent issues in both clinical and preclinical sepsis. The increasing recognition for the need to account for sex and gender in biomedical research brings a unique set of challenges and requires researchers to adopt best practices when conducting and communicating sex- and gender-based research. This may be of particular importance in sepsis, given the potential contribution of sex bias in the failures of translational sepsis research in adults and neonates. Clinical evidence of sex-dependent differences in sepsis is equivocal. Since clinical studies are limited to observational data and confounded by a multitude of factors, preclinical studies provide a unique opportunity to investigate sex differences in a controlled, experimental environment. Numerous preclinical studies have suggested that females may experience favorable outcomes in comparison with males. The underlying mechanistic evidence for sex-dependent differences in sepsis and other models of shock (e.g., trauma-hemorrhage) largely centers around the beneficial effects of estrogen. Other mechanisms such as the immunosuppressive role of testosterone and X-linked mosaicism are also thought to contribute to observed sex- and gender-dependent differences in sepsis. Significant knowledge gaps still exist in this field. Future investigations can address these gaps through careful consideration of sex and gender in clinical studies, and the use of clinically accurate preclinical models that reflect sex differences. A better understanding of sex-and gender-dependent differences may serve to increase translational research success.
在本综述中，我们概述了临床和临床前脓毒症中与性别相关的问题。生物医学研究中越来越认识到需要考虑性别因素，这带来了一系列独特的挑战，要求研究人员在开展和交流基于性别的研究时采用最佳实践。鉴于性别偏见可能导致成人和新生儿脓毒症转化研究失败，这在脓毒症研究中可能尤为重要。脓毒症中性别差异的临床证据并不明确。由于临床研究仅限于观察性数据且受多种因素混淆，临床前研究提供了一个在可控实验环境中研究性别差异的独特机会。大量临床前研究表明，与男性相比，女性可能有更好的预后。脓毒症及其他休克模型（如创伤性出血）中性别差异的潜在机制证据主要围绕雌激素的有益作用。其他机制，如睾酮的免疫抑制作用和X连锁嵌合体，也被认为与脓毒症中观察到的性别差异有关。该领域仍存在重大知识空白。未来的研究可以通过在临床研究中仔细考虑性别因素以及使用反映性别差异的临床准确的临床前模型来填补这些空白。更好地理解性别差异可能有助于提高转化研究的成功率。
