Anesthetic gas sevoflurane postconditioning alleviates cognitive impairment induced by hemorrhagic shock and resuscitation

Hu, Su1,#; Huang, Xiaoci2,#; Wan, Xiaojing2; Niu, Zhilun2; Hu, Xianwen2,*

Author Information

1Department of Otolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China

2Department of Anesthesiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China

*Correspondence to: Xianwen Hu, MD, huxianwen001@163.com

#Both authors contributed equally to this work.

Funding:The study was supported by Natural Science Foundation of Anhui Province (No. 2408085MH212), the National Natural Science Foundation Incubation Program of The Second Affiliated Hospital of Anhui Medical University (No. 2020GQFY01), the Major Scientific Research Project of Natural Science in Universities of Anhui Province (No. KJ2021ZD0030), and the Key Research and Development Project of Anhui Province (No. 2022e07020045).

Abstract

Sevoflurane is a new type of halogen inhalation anesthetic gas with a rapid induction and emergence. It is widely used for general anesthesia. Previous studies have demonstrated that sevoflurane postconditioning alleviates cerebral ischemia–reperfusion injury and enhances the tolerance of the brain to ischemia and hypoxia. However, whether sevoflurane postconditioning can reduce cerebral ischemia–reperfusion injury caused by hemorrhagic shock and resuscitation and the underlying mechanism are unclear. The present study established cerebral ischemia–reperfusion injury models through an in vivo hemorrhagic shock and resuscitation method in C57BL/6 mice and an in vitro oxygen–glucose deprivation/reoxygenation method in HT22 cells. After hemorrhagic shock and resuscitation treatment, the mice developed significant spatial learning and memory impairments accompanied by aggravated cerebral infarction, whereas sevoflurane postconditioning significantly improved these effects. After in vitro oxygen–glucose deprivation/reoxygenation, the survival rate of HT22 cells was decreased, the apoptosis rate was increased, the expression of silent information regulatory factor 1 was decreased, and the expressions of hypoxia-inducible factor 1α, NOD-like receptor protein 3, gasdermin D, caspase-1, and interleukin-1β were increased. Sevoflurane postconditioning inhibited oxygen–glucose deprivation/reoxygenation-induced changes. Following silent information regulatory factor 1 knockdown by small interfering RNA, the cytoprotective effects of sevoflurane postconditioning were significantly attenuated. These findings suggest that the anesthetic gas sevoflurane postconditioning ameliorates hemorrhagic shock and resuscitation-induced cognitive impairment. This may be mediated by the silent information regulatory factor 1/hypoxia-inducible factor 1α/NOD-like receptor protein 3 pathway.

摘要

七氟烷是一种新型卤化吸入麻醉气体，具有诱导和苏醒迅速的特点，广泛用于全身麻醉。既往研究证实，七氟烷后处理能够减轻脑缺血-再灌注损伤，并增强大脑对缺血缺氧的耐受性。然而，七氟烷后处理能否减轻失血性休克复苏所致脑缺血-再灌注损伤及其潜在机制尚不清楚。本研究通过体内C57BL/6小鼠失血性休克复苏模型和体外HT22细胞氧糖剥夺/复氧模型构建脑缺血-再灌注损伤模型。结果显示，失血性休克复苏处理后，小鼠出现显著的空间学习和记忆功能障碍，并伴有脑梗死加重，而七氟烷后处理显著改善了这些效应。在体外氧糖剥夺/复氧处理后，HT22细胞存活率下降、凋亡率上升，沉默信息调节因子1表达降低，而缺氧诱导因子1α、NOD样受体蛋白3、gasdermin D、caspase-1和白细胞介素-1β表达升高。七氟烷后处理抑制了氧糖剥夺/复氧诱导的这些变化。通过小干扰RNA敲低沉默信息调节因子1后，七氟烷后处理的细胞保护作用显著减弱。这些发现表明，麻醉气体七氟烷后处理能够改善失血性休克复苏诱导的认知功能障碍，其作用可能通过沉默信息调节因子1/缺氧诱导因子1α/NOD样受体蛋白3通路介导。