Alpha-linolenic acid protects against lipopolysaccharide-induced acute lung injury through anti-inflammatory and anti-oxidative pathways
Alpha-linolenic acid protects against lipopolysaccharide-induced acute lung injury through anti-inflammatory and anti-oxidative pathways
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α-亚麻酸通过抗炎和抗氧化途径预防脂多糖诱导的急性肺损伤
DOI：
10.1016/j.micpath.2020.104077
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发表时间：
2020-05-01
影响因子：
3.8
通讯作者：
Li, Jinbao
中科院分区：
文献类型：
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作者：
Zhu, Xuejiao;Wang, Bing;Li, Jinbao
α-亚麻酸（ALA）是多不饱和脂肪酸（PUFAs）的重要组成部分，具有很强的抗炎作用。迄今为止，ALA对急性肺损伤（ALI）的影响仍不清楚。本研究旨在探讨ALA对LPS诱导的急性肺损伤的保护作用及其机制。采用脂多糖（LPS，1 mg/kg）建立ALI动物模型。结果发现，ALA预处理可显著降低肺湿/干重比和支气管肺泡灌洗液（BALF）中蛋白质浓度。ALA可明显减轻总细胞和中性粒细胞的浸润，同时增加巨噬细胞的数量。ALA显著抑制促炎细胞因子包括肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-1 β（IL-1 β）的分泌，并增加抗炎细胞因子。此外，我们还发现LPS诱导的ALI中髓过氧化物酶（MPO）和丙二醛（MDA）水平显著升高，而谷胱甘肽（GSH）和超氧化物歧化酶（SOD）活性降低，ALA可逆转这一变化。ALA可减轻LPS诱导的组织病理学改变和细胞凋亡。此外，ALA显著抑制ALI中I κ B α的磷酸化和NF-κ B（p65）的活化。ALA对LPS诱导的ALI小鼠有明显的抗炎作用。NF-κ B B通路可能参与ALA介导的保护作用。
Alpha-linolenic acid (ALA), an important component of polyunsaturated fatty acids (PUFAs), possesses potent anti-inflammatory properties. To date, the effects of ALA on acute lung injury (ALI) remains unknown. This study was designed to investigate the potential protective effects of ALA on LPS-induced ALI and the underpinning mechanisms. An animal model of ALI was established via intratracheally injection of lipopolysaccharide (LPS, 1 mg/kg). We found that lung wet/dry weight ratio and protein concentration in Bronchoalveolar lavage fluid (BALF) were dramatically decreased by ALA pretreatment. Treatment with ALA significantly alleviated the infiltration of total cells and neutrophils, while increased the number of the macrophages. ALA significantly inhibited the secretion of proinflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) and increased anti-inflammatory cytokine. Moreover, we found that the levels of myeloperoxidase (MPO) and malondialdehyde (MDA) were highly increased in LPS-induced ALI, while the activities of glutathione (GSH) and superoxide dismutase (SOD) were decreased, which were reversed by ALA. ALA attenuated LPS-induced histopathological changes and apoptosis. Furthermore, ALA significantly inhibited the phosphorylation of I kappa B alpha and NF-kappa B (p65) activation in ALI. ALA showed anti-inflammatory effects in mice with LPS-induced ALI. NF-kappa B pathway may be involved in ALA mediated protective effects.