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橙皮苷对脂多糖诱导的小鼠急性肺损伤的治疗作用。

The therapeutic effects of Jaceosidin on lipopolysaccharide-induced acute lung injury in mice.

机构信息

College of Pharmaceutical Science, Soochow University, Suzhou 215123, People's Republic of China.

College of Pharmaceutical Science, Soochow University, Suzhou 215123, People's Republic of China; Pharmacy Department of BOE Hefei Digital Hospital, Hefei 230000, People's Republic of China.

出版信息

J Pharmacol Sci. 2019 Jul;140(3):228-235. doi: 10.1016/j.jphs.2019.07.004. Epub 2019 Jul 18.

DOI:10.1016/j.jphs.2019.07.004
PMID:31358372
Abstract

Acute lung injury (ALI) results from various factors including uncontrolled pulmonary inflammation, oxidative damage and the over-activated complement with high mortality rates. Jaceosidin was a flavonoid compound with significant anti-complement activity. We aimed to investigate the therapeutic effects of Jaceosidin on ALI induced by lipopolysaccharide (LPS). Mice were orally administrated with Jaceosidin (15, 30 and 60 mg/kg) after LPS challenge. 24 h after LPS challenge, Jaceosidin could significantly decrease the lung wet-to-dry weight (W/D) ratio and the protein concentration in bronchoalveolar lavage fluid (BALF). Jaceosidin could down-regulate the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β), together with up-regulation the levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) in BALF. Jaceosidin could significantly decrease the levels of myeloperoxidase (MPO), cyclooxygenase-2 (COX-2) and nuclear factor-κB (NF-κB), COX-2 mRNA and NF-κB p65 mRNA together with increasing the activity of catalase (CAT). Additionally, Jaceosidin attenuated lung histopathological changes, inhibited the expressions of COX-2 and NF-κB p65 and reduced complement deposition with decreasing the levels of complement 3 (C3) and complement 3c (C3c) in serum. These data suggest that Jaceocidin may dampen the inflammatory response and decrease the levels of complement together with the antioxidant activity following LPS-induced ALI.

摘要

急性肺损伤(ALI)是由多种因素引起的,包括失控的肺部炎症、氧化损伤和过度激活的补体,其死亡率很高。乔松素是一种具有显著抗补体活性的黄酮类化合物。我们旨在研究乔松素对脂多糖(LPS)诱导的 ALI 的治疗作用。LPS 攻击后,小鼠经口给予乔松素(15、30 和 60mg/kg)。LPS 攻击后 24 小时,乔松素可显著降低肺湿重/干重(W/D)比和支气管肺泡灌洗液(BALF)中的蛋白浓度。乔松素可下调 BALF 中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β)的水平,同时上调白细胞介素-4(IL-4)和白细胞介素-10(IL-10)的水平。乔松素可显著降低髓过氧化物酶(MPO)、环加氧酶-2(COX-2)和核因子-κB(NF-κB)、COX-2 mRNA 和 NF-κB p65 mRNA 的水平,同时增加过氧化氢酶(CAT)的活性。此外,乔松素减轻了肺组织病理学变化,抑制了 COX-2 和 NF-κB p65 的表达,并减少了补体沉积,同时降低了血清中补体 3(C3)和补体 3c(C3c)的水平。这些数据表明,乔松素可能通过抑制炎症反应和降低补体水平以及发挥抗氧化活性,减轻 LPS 诱导的 ALI。

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