Aprepitant alleviates post-stroke pneumonia in a mouse model of middle cerebral artery occlusion.

Zhihui Xie, Minghui Xin, Fatao Yu, Xiaolin Zhu
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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 post-stroke pneumonia 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 h, 48 h, and 72 h post-stroke. On the other hand, different concentrations of aprepitant (0.5, 1, 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-h post-stroke, 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 post-stroke pneumonia in mice suggesting its potential therapeutic use in the clinic.
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阿瑞匹坦可减轻大脑中动脉闭塞小鼠模型卒中后肺炎。
物质 P 升高可用于预测脑梗塞第一周的早期死亡率。本研究探讨了是否可以利用物质 P 受体阻断剂阿普瑞坦来缓解卒中后肺炎。本研究以 C57BL/6J 雄性小鼠为对象,构建了大脑中动脉闭塞(MCAO)的腔内单丝模型,并检测了卒中后 24 h、48 h 和 72 h 采集的支气管肺泡灌洗液(BALF)和肺组织匀浆中 P 物质的相对表达。另一方面,将不同浓度的阿普瑞坦(0.5、1、2 毫克/千克)雾化并吸入 MCAO 小鼠体内。中风后72小时,在收集的BALF和肺组织匀浆中检测到炎症细胞因子和细菌负荷,组织学检查显示肺损伤。服用阿瑞匹坦可减少 BALF 中的总蛋白、总细胞、中性粒细胞和巨噬细胞。阿瑞匹坦还能降低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。总之,阿瑞匹坦可减轻小鼠卒中后肺炎,这表明它有可能用于临床治疗。
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