滨蒿总黄酮调控Nrf2/HO-1信号通路改善小鼠急性肺损伤的作用机制

doi:10.19803/j.1672-8629.20260530

摘要/Abstract

摘要： 目的研究滨蒿总黄酮通过调控核转录因子E2相关因子（Nrf2）/血红素加氧酶-1（HO-1）信号通路改善小鼠急性肺损伤（ALI）的作用机制。方法 90只ICR小鼠随机分为6组,包括正常组,模型组,地塞米松组（2.5 mg·kg^-1）,滨蒿总黄酮低、中、高剂量组（100、200、400 mg·kg^-1）,每组15只。各给药组小鼠分别经灌胃给予对应药物,每日1次,连续5 d。除正常组外,其余各组小鼠采用鼻腔滴入脂多糖（LPS）的方法诱导ALI小鼠模型。给予LPS 16 h后取材,检测各组小鼠肺组织湿/干重比,苏木精-伊红（HE）染色观察肺组织病理改变,ELISA法检测肺泡灌洗液（BALF）内细胞间黏附分子1（ICAM-1）、肿瘤坏死因子-α（TNF-α）含量,BCA法测定BALF中蛋白浓度,生化法检测肺组织还原型谷胱甘肽（GSH）、丙二醛（MDA）含量及超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、髓过氧化物酶（MPO）活性,RT-qPCR检测肺组织Kelch样ECH相关蛋白1（Keap-1）、Nrf2、HO-1、醌氧化还原酶-1（NQO1）mRNA表达,Western Blot检测肺组织Keap-1、Nrf2、HO-1蛋白表达。结果与模型组相比,滨蒿总黄酮组小鼠肺组织湿/干重比显著降低（P<0.05,P<0.01）,肺组织病理损伤明显改善,BALF中ICAM-1、TNF-α和蛋白浓度显著降低（P<0.01）,肺组织GSH含量、SOD和CAT活性显著升高（P<0.05,P<0.01）,而MDA含量和MPO活性显著降低（P<0.05）,肺组织Keap-1 mRNA及蛋白表达显著降低（P<0.05）,Nrf2、HO-1 mRNA及蛋白表达显著升高（P<0.05,P<0.01）。结论滨蒿总黄酮可能通过调控Nrf2/HO-1信号通路,减轻炎症反应并提高抗氧化能力,从而改善ALI。

关键词: 滨蒿总黄酮, 急性肺损伤, 核转录因子E2相关因子/血红素加氧酶-1信号通路, 氧化应激

Abstract: Objective To explore the mechanism by which total flavonoids of Artemisia scoparia (TFA) ameliorate acute lung injury (ALI) in mice by regulating the signaling pathway of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1). Methods A total of 90 ICR mice were randomly divided into a control group, model group, dexamethasone group (2.5 mg·kg^-1), TFA low dose, medium dose, and high dose groups (100, 200, 400 mg·kg^-1), with 15 mice in each group. The administration groups were orally administered with corresponding drugs once a day for 5 days. An ALI model was induced by nasal instillation of lipopolysaccharide (LPS) in these groups except the control group. Samples were collected 16 hours after LPS administration, and the lung weight wet/dry ratio was determined for mice in each group. The pathological changes of lung tissues were examined by HE staining. The protein content in BALF was measured using the BCA method. The levels of superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO), malondialdehyde (MDA) and glutathione (GSH) in lung tissues were detected using colorimetry. The mRNA expressions of Kelch-like ECH-associated protein 1(Keap-1), Nrf2, HO-1, quinone oxidoreductase 1 (NQO1) in lung tissues were detected by RT-qPCR. The protein expressions of Keap-1, Nrf2 and HO-1 in lung tissues were determined by Western blotting. Results Compared with the model group, the lung wet/dry weight ratio was significantly decreased in the TFA group (P<0.05, P<0.01), pathological injury of lung tissues was significantly improved, and the concentrations of ICAM-1, TNF-α and protein in BALF were significantly deduced (P<0.01). The content of GSH and the activities of SOD and CAT in lung tissues were significantly increased (P<0.05, P<0.01), while the content of MDA and the activities of MPO were markedly decreased (P<0.05). The expression of Keap-1 mRNA and protein in lung tissues was significantly decreased (P<0.05), while the expressions of Nrf2 and HO-1 mRNA and protein were significantly increased (P<0.05, P<0.01). Conclusion TFA may alleviate inflammatory responses and enhance antioxidant capacity by regulating the Nrf2/HO-1 signaling pathway, thereby improving ALI.

Key words: Total Flavonoids of Artemisia scoparia (TFA), Acute Lung Injury, Nrf2/HO-1 Signaling Pathway, Oxidative Stress

中图分类号:

R951
R994.11

刘燕, 史玉柱, 徐磊, 王雪. 滨蒿总黄酮调控Nrf2/HO-1信号通路改善小鼠急性肺损伤的作用机制[J]. 中国药物警戒, 2026, 23(9): 997-1004.

Liu Yan, Shi Yuzhu, Xu Lei, Wang Xue. Mechanisms of total flavonoids of Artemisia scoparia against acute lung injury by regulating Nrf2/HO-1 signaling pathway[J]. Chinese Journal of Pharmacovigilance, 2026, 23(9): 997-1004.

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