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瑞马唑仑对脓毒症诱导的急性呼吸窘迫综合征(ARDS)保护作用的初步研究

Preliminary study on the protective effect of remazolam against sepsis-induced acute respiratory distress syndrome (ARDS).

作者信息

Gao Xiaoxin, Zhang Rujun, Wang Zhenzhou, Chen Qingan, Lei Zhenlin, Yang Yanan, Tian Jia

机构信息

Intensive Medical Unit, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China.

Department of Cardiology, Hainan Province Clinical Medical Center, Hainan General Hospital; Hainan Affiliated Hospital of Hainan Medical University, Haikou, China.

出版信息

PeerJ. 2024 Apr 18;12:e17205. doi: 10.7717/peerj.17205. eCollection 2024.

Abstract

BACKGROUND

Sepsis can disrupt immune regulation and lead to acute respiratory distress syndrome (ARDS) frequently. Remazolam, a fast-acting hypnotic drug with superior qualities compared to other drugs, was investigated for its potential protective effects against sepsis-induced ARDS.

METHODS

Forty Sprague-Dawley rats were randomly divided into four groups, including the sepsis + saline group, sham operation + saline group, sham operation + remazolam group and the sepsis + remazolam group. Lung tissues of rats were extracted for HE staining to assess lung damage, and the wet weight to dry weight (W/D) ratio was calculated. The levels of proinflammatory factors, anti-inflammatory factors, CD4+ and CD8+ T cells in peripheral blood, MDA, MPO, and ATP in the lung tissue were measured by using ELISA. Western blotting was performed to determine the protein expression of HMGB1 in lung tissues.

RESULTS

In comparison to the sham operation + saline and sham operation + remazolam groups, the sepsis + saline group exhibited significantly higher values for W/D ratio, lung damage score, IL-1β, IL-6, TNF-α, PCT, CRP, MDP and MPO, while exhibiting lower levels of CD4+ and CD8+ T lymphocytes, PaO, PCO, and ATP. The rats in the sepsis + saline group displayed ruptured alveolar walls and evident interstitial lung edema. However, the rats in the sepsis + remazolam group showed improved alveolar structure. Furthermore, the HMGB1 protein expression in the sepsis + remazolam group was lower than the sepsis + saline group.

CONCLUSION

Remazolam can alleviate the inflammatory response in infected rats, thereby alleviating lung injury and improving immune function, which may be attributed to the reduction in HMGB1 protein expression.

摘要

背景

脓毒症可扰乱免疫调节并常常导致急性呼吸窘迫综合征(ARDS)。瑞马唑仑是一种速效催眠药物,与其他药物相比具有优越特性,本研究探讨其对脓毒症诱导的ARDS的潜在保护作用。

方法

40只Sprague-Dawley大鼠随机分为四组,包括脓毒症+生理盐水组、假手术+生理盐水组、假手术+瑞马唑仑组和脓毒症+瑞马唑仑组。提取大鼠肺组织进行HE染色以评估肺损伤,并计算湿重与干重(W/D)比值。采用ELISA法检测外周血中促炎因子、抗炎因子、CD4+和CD8+T细胞水平,以及肺组织中丙二醛(MDA)、髓过氧化物酶(MPO)和三磷酸腺苷(ATP)水平。采用蛋白质免疫印迹法检测肺组织中高迁移率族蛋白B1(HMGB1)的蛋白表达。

结果

与假手术+生理盐水组和假手术+瑞马唑仑组相比,脓毒症+生理盐水组的W/D比值、肺损伤评分、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、降钙素原(PCT)、C反应蛋白(CRP)、髓样分化蛋白(MDP)和MPO显著更高,而CD4+和CD8+T淋巴细胞、动脉血氧分压(PaO)、动脉血二氧化碳分压(PCO)和ATP水平更低。脓毒症+生理盐水组大鼠出现肺泡壁破裂和明显的间质性肺水肿。然而,脓毒症+瑞马唑仑组大鼠的肺泡结构有所改善。此外,脓毒症+瑞马唑仑组的HMGB1蛋白表达低于脓毒症+生理盐水组。

结论

瑞马唑仑可减轻感染大鼠的炎症反应,从而减轻肺损伤并改善免疫功能,这可能归因于HMGB1蛋白表达的降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e88/11032653/ef206d5e65bb/peerj-12-17205-g001.jpg

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