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苑萌,董慧文,刘佳丽,冯学辉,韩宝华,韩树池,张志斌,卢晶.麻黄水提物减轻脂多糖诱导急性肺损伤的作用及机制研究[J].湖南中医药大学学报,2023,43(12):2185-2190[点击复制] |
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麻黄水提物减轻脂多糖诱导急性肺损伤的作用及机制研究 |
苑萌,董慧文,刘佳丽,冯学辉,韩宝华,韩树池,张志斌,卢晶 |
(河北北方学院附属第一医院急诊科, 河北 张家口 075000) |
摘要: |
目的 研究麻黄水提物通过活性氧(reactive oxygen species,ROS)/硫氧还蛋白相互作用蛋白(thioredoxin-interacting protein,TXNIP)/Nod样受体蛋白3(Nod like receptor protein 3,NLRP3)通路减轻脂多糖(lipopolysaccharide,LPS)诱导急性肺损伤(acute lung injury,ALI)的作用及机制。方法 雄性SD大鼠随机分为正常对照组、模型组、麻黄水提物(400 mg/kg)组、三甲胺N-氧化物(trimethylamine N-oxide,TMAO,110 mg/kg)组、麻黄水提物(400 mg/kg)+TMAO(110 mg/kg)组,灌胃给药10 d后采用腹腔注射LPS(5 mg/kg)的方法建立LPS诱导ALI模型。造模后6 h,检测肺组织病理改变,支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中炎症细胞分类,血清及BALF中白细胞介素(interleukin,IL)-1β、IL-18、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)含量,肺组织中丙二醛(malondialdehyde,MDA)、总抗氧化力(total antioxidant capacity,T-AOC)含量、ROS活力及TXNIP、NLRP3的表达水平。结果 模型对照组大鼠出现肺组织内炎症细胞浸润、肺泡间隔增厚的病理改变,BALF中性粒细胞、淋巴细胞、嗜酸性粒细胞的数量,血清及BALF中IL-1β、IL-18、TNF-α含量,肺组织中MDA含量、ROS活力及TXNIP、NLRP3的表达水平均高于正常对照组(P<0.05);肺组织中T-AOC含量低于正常对照组(P<0.05)。麻黄水提物组大鼠肺组织的病理改变较模型对照组改善,BALF中性粒细胞、淋巴细胞、嗜酸性粒细胞的数量,血清及BALF中IL-1β、IL-18、TNF-α含量,肺组织中MDA含量、ROS活力及TXNIP、NLRP3的表达水平均低于模型对照组(P<0.05);肺组织中T-AOC含量高于模型对照组(P<0.05)。麻黄水提物+TMAO组大鼠肺组织的病理改变较麻黄水提物组加重,BALF中性粒细胞、淋巴细胞、嗜酸性粒细胞的数量,血清及BALF中IL-1β、IL-18、TNF-α含量,肺组织中MDA含量、ROS活力及TXNIP、NLRP3的表达水平均高于麻黄水提物组(P<0.05);肺组织中T-AOC含量低于麻黄水提物组(P<0.05)。结论 麻黄水提物可减轻LPS诱导ALI,并抑制炎症反应和氧化应激反应,其可能的分子机制与抑制ROS/TXNIP/NLRP3通路有关。 |
关键词: 急性肺损伤 麻黄水提物 活性氧 硫氧还蛋白相互作用蛋白 Nod样受体蛋白3 |
DOI:10.3969/j.issn.1674-070X.2023.12.007 |
投稿时间:2023-05-26 |
基金项目:河北省卫生健康委员会科研基金项目(20231403)。 |
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Effects and mechanism of ephedra aqueous extract on alleviating lipopolysaccharide-induced acute lung injury |
YUAN Meng,DONG Huiwen,LIU Jiali,FENG Xuehui,HAN Baohua,HAN Shuchi,ZHANG Zhibin,LU Jing |
(Department of Emergency, The First Hospital of Hebei North University, Zhangjiakou, Hebei 075000, China) |
Abstract: |
Objective To investigate the effects and mechanism of ephedra aqueous extract on alleviating lipopolysaccharide(LPS)-induced acute lung injury(ALI) by the reactive oxygen species(ROS)/thioredoxin-interacting protein(TXNIP)/Nod like receptor protein 3(NLRP3) pathways.Methods Male SD rats were randomized into normal control, model, ephedra aqueous extract(400 mg/kg), trimethylamine N-oxide(TMAO, 110 mg/kg), and ephedra aqueous extract(400 mg/kg) + TMAO(110 mg/kg) groups. After 10 d of gavage, LPS-induced ALI model was established by intraperitoneal injection of LPS(5 mg/kg). Six hours after modeling, pathological changes in lung tissue, classification of inflammatory cells in bronchoalveolar lavage fluid(BALF), the content of interleukin(IL)-1β, IL-18, tumor necrosis factor-α(TNF-α) in serum and BALF, and the content of malondialdehyde(MDA), total antioxidant capacity(T-AOC), ROS activity, and the expression levels of TXNIP and NLRP3 in lung tissue were determined.Results The model control group rats showed pathological changes including infiltration of inflammatory cells in lung tissue, thickening of alveolar septa, and the number of neutrophils, lymphocytes, and eosinophils in BALF, the content of IL-1β, IL-18, TNF-α in serum and BALF, and the content of MDA, ROS activity, and the expression levels of TXNIP and NLRP3 in lung tissue were higher than those in the normal control group(P<0.05), while the T-AOC content in lung tissue was lower than that in the normal control group(P<0.05). The pathological changes in the lung tissue of ephedra aqueous extract group were significantly improved compared with the model control group. The number of neutrophils, lymphocytes, eosinophils in BALF, the content of IL-1β, IL-18, TNF-α in serum and BALF, and the content of MDA, ROS activity, and the expression levels of TXNIP and NLRP3 in lung tissue were lower than those in the model control group(P<0.05), while the T-AOC content in lung tissue was higher than that in the model control group(P<0.05).The pathological changes in the lung tissue of the ephedra aqueous extract + TMAO group were more severe than those in the ephedra aqueous extract group, the number of neutrophils, lymphocytes, eosinophils in BALF, the content of IL-1β, IL-18, TNF-αin serum and BALF, and the content of MDA, ROS activity, and the expression levels of TXNIP and NLRP3 in lung tissue were higher than those in the ephedra aqueous extract group(P<0.05), while the T-AOC content in lung tissue was lower than that in the ephedra aqueous extract group(P<0.05).Conclusion Ephedra aqueous extract can alleviate LPS-induced ALI and inhibit inflammatory and oxidative stress responses, and its possible mechanism is related to the inhibition of the ROS/TXNIP/NLRP3 pathways. |
Key words: acute lung injury ephedra aqueous extract reactive oxygen species thioredoxin interacting protein Nod like receptor protein 3 |
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