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柚皮苷通过上调脂多糖/香烟烟雾诱导的小鼠水通道蛋白 1 抑制气道炎症和改善肺血管内皮通透性。

Naringin suppressed airway inflammation and ameliorated pulmonary endothelial hyperpermeability by upregulating Aquaporin1 in lipopolysaccharide/cigarette smoke-induced mice.

机构信息

School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China; Zhejiang Provincial Laboratory of Experimental Animal's & Nonclinical Laboratory Studies, Hangzhou Medical College, Hangzhou, China.

School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.

出版信息

Biomed Pharmacother. 2022 Jun;150:113035. doi: 10.1016/j.biopha.2022.113035. Epub 2022 Apr 28.

DOI:10.1016/j.biopha.2022.113035
PMID:35658207
Abstract

Naringin is one of the natural flavonoids extracted from many Chinese medicines. It ameliorates endothelial dysfunctions in atherosclerosis, diabetes, and cardiovascular diseases through free radical scavenging and antioxidant activities. The aim of the present study was to investigate the protective effects of naringin against pulmonary endothelial permeability in addition to airway inflammation in lipopolysaccharide/cigarette smoke (LPS/CS)-induced chronic obstructive pulmonary disease (COPD) mice.The COPD mice were exposed to LPS twice through intranasal inhalation and then to cigarette smoke daily for 6 weeks. The mice were orally administrated with naringin at doses of 40 or 80 mg/kg one hour before cigarette smoke exposure since the first day of the experiment. Naringin significantly alleviated pulmonary histopathological injury, and suppressed inflammatory cell infiltration and cytokine release in bronchoalveolar lavage fluid. Naringin decreased fluorescence intensity of Evans Blue in the lung tissues, and elevated the expression levels of tight junctional proteins. Meanwhile, naringin decreased neutrophil/lymphocyte/platelet counts and MDA content in blood, and upregulated Aquaporin1 (AQP1) in the lung tissues. However, the effect of naringin on airway inflammation and pulmonary endothelial permeability was inhibited in LPS/CS-treatment AQP1 deficiency mice. These results indicated that naringin attenuated LPS/CS-induced airway inflammatory and pulmonary hyperpermeability via upregulating AQP1 expression.

摘要

柚皮苷是从多种中药中提取的天然类黄酮之一。它通过清除自由基和抗氧化活性,改善动脉粥样硬化、糖尿病和心血管疾病中的血管内皮功能障碍。本研究旨在探讨柚皮苷对脂多糖/香烟烟雾(LPS/CS)诱导的慢性阻塞性肺疾病(COPD)小鼠肺内皮通透性的保护作用,以及对气道炎症的作用。COPD 小鼠通过鼻腔内吸入两次 LPS,然后每天接受香烟烟雾暴露,共 6 周。从实验的第一天开始,柚皮苷以 40 或 80mg/kg 的剂量在香烟烟雾暴露前 1 小时口服给予小鼠。柚皮苷显著减轻了肺组织的组织病理学损伤,并抑制了支气管肺泡灌洗液中炎性细胞浸润和细胞因子释放。柚皮苷降低了肺组织中 Evans Blue 的荧光强度,并上调了紧密连接蛋白的表达水平。同时,柚皮苷降低了血液中的中性粒细胞/淋巴细胞/血小板计数和 MDA 含量,并上调了肺组织中的水通道蛋白 1(AQP1)。然而,在 LPS/CS 处理 AQP1 缺陷小鼠中,柚皮苷对气道炎症和肺内皮通透性的作用被抑制。这些结果表明,柚皮苷通过上调 AQP1 的表达来减轻 LPS/CS 诱导的气道炎症和肺高通透性。

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