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鼻腔内姜黄素和地塞米松联合应用可改善脂多糖暴露的哮喘加重中炎症小体(NLRP3)的激活。

Intranasal curcumin and dexamethasone combination ameliorates inflammasome (NLRP3) activation in lipopolysachharide exposed asthma exacerbations.

机构信息

Department of Zoology, MMV, Banaras Hindu University, Varanasi 221005, India.

Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India.

出版信息

Toxicol Appl Pharmacol. 2022 Feb 1;436:115861. doi: 10.1016/j.taap.2021.115861. Epub 2022 Jan 5.

Abstract

The inflammasome NOD-like receptor (NLR) family, the pyrin domain containing 3 (NLRP3) is closely associated with exacerbation of asthma as endotoxin (lipopolysaccharide, LPS) is one of its activators present in the environment. Present study is undertaken to investigate anti-inflammatory effects of a well known phytochemical, curcumin, which might regulate LPS exposed asthma exacerbations by modulating NLRP3 activation if given through intranasal route. Balb/c mice were sensitized with intraperitoneal injection of OVA (Ovalbumin; 100 μg of OVA with alum) from day 1 to 8 and exposed to LPS with 1% OVA aerosol from day 9 to 15. LPS (0.1 μg) was given an hour before sensitization and OVA-aerosol challenge. Significant decrease in inflammatory cell recruitment and restoration of structural changes in lungs, alterations in mRNA and protein expressions of TLR-4, NF-κB, NLRP3, Caspase-1, IL-1β, MMP-9, IL-5 and IL-17 in intranasal curcumin alone and corticosteroid combined pretreatment group.

摘要

炎症小体 NOD 样受体 (NLR) 家族,富含吡喃结构域蛋白 3 (NLRP3) 与哮喘恶化密切相关,内毒素 (脂多糖,LPS) 是其在环境中的一种激活剂。本研究旨在探讨一种众所周知的植物化学物质姜黄素的抗炎作用,通过鼻内途径给药可能通过调节 NLRP3 激活来调节 LPS 暴露引起的哮喘恶化。Balb/c 小鼠从第 1 天到第 8 天通过腹腔注射 OVA(卵清蛋白;100μg OVA 与明矾)进行致敏,并从第 9 天到第 15 天用 1%OVA 气溶胶暴露于 LPS。LPS(0.1μg)在致敏前 1 小时给予,OVA-气溶胶挑战。单独鼻内姜黄素和皮质类固醇联合预处理组可显著减少炎症细胞募集,并恢复肺的结构变化,改变 TLR-4、NF-κB、NLRP3、半胱天冬酶-1、IL-1β、MMP-9、IL-5 和 IL-17 的 mRNA 和蛋白表达。

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