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阿瑞匹坦减轻大脑中动脉闭塞模型小鼠的卒中相关性肺炎。

Aprepitant Alleviates Poststroke Pneumonia in a Mouse Model of Middle Cerebral Artery Occlusion.

机构信息

Department of Infectious Disease, Zibo Central Hospital, Zibo, People's Republic of China.

Department of Clinical Laboratory, Zibo Central Hospital, Zibo, People's Republic of China.

出版信息

Rejuvenation Res. 2024 Jun;27(3):102-109. doi: 10.1089/rej.2024.0011. Epub 2024 May 13.

DOI:10.1089/rej.2024.0011
PMID:38666697
Abstract

Elevated substance P can be utilized to predict early mortality during the first week of cerebral infarction. Whether aprepitant, a substance P receptor blocker could be utilized to alleviate poststroke pneumonia which is investigated in this study. Intraluminal monofilament model of middle cerebral artery occlusion (MCAO) was constructed in C57BL/6J male mice, and the relative expression of substance P was detected in collected bronchoalveolar lavage fluid (BALF) and lung tissue homogenate at 24 hours, 48 hours, and 72 hours poststroke. On the other hand, different concentrations of aprepitant (0.5, 1, and 2 mg/kg) were atomized and inhaled into MCAO mice. Inflammation cytokines and bacterial load were detected in collected BALF and lung tissue homogenate at 72-hour poststroke, and lung injury was revealed by histological examination. Aprepitant administration decreased total proteins, total cells, neutrophils, and macrophages in BALF. The concentrations of interleukin (IL)-6, IL-1β, tumor necrosis factor-α, interferon γ, monocyte chemoattractant protein-1, and IL-10 in lung tissue homogenates were also diminished by the administration of aprepitant. In conclusion, aprepitant could attenuate poststroke pneumonia in mice suggesting its potential therapeutic use in the clinic.

摘要

升高的 P 物质可用于预测脑梗死第一周的早期死亡率。本研究旨在探讨 P 物质受体拮抗剂阿瑞匹坦是否可用于缓解脑卒中后肺炎。构建 C57BL/6J 雄性小鼠大脑中动脉闭塞(MCAO)的管内单丝模型,并在脑卒中后 24 小时、48 小时和 72 小时收集支气管肺泡灌洗液(BALF)和肺组织匀浆中检测 P 物质的相对表达。另一方面,将不同浓度的阿瑞匹坦(0.5、1 和 2 mg/kg)雾化吸入 MCAO 小鼠。在脑卒中后 72 小时收集 BALF 和肺组织匀浆,检测炎症细胞因子和细菌负荷,并通过组织学检查显示肺损伤。阿瑞匹坦给药可降低 BALF 中的总蛋白、总细胞、中性粒细胞和巨噬细胞。肺组织匀浆中白细胞介素(IL)-6、IL-1β、肿瘤坏死因子-α、干扰素-γ、单核细胞趋化蛋白-1 和 IL-10 的浓度也因阿瑞匹坦的给药而降低。总之,阿瑞匹坦可减轻小鼠脑卒中后肺炎,提示其在临床上具有潜在的治疗用途。

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