苏黄止咳胶囊可通过作用AhR-Nrf2通路改善小鼠感染后咳嗽
2022/01/28
摘要
背景:苏黄止咳胶囊(SH capsule)是典型的中药复方，临床上广泛用于治疗感染后咳嗽(PIC)。我们前期研究表明，SH胶囊对咳嗽变异性哮喘(CVA)、痰梗阻、气道重塑均有显著的改善作用。
目的:本研究旨在探讨苏黄止咳胶囊对小鼠PIC的改善作用及其可能机制。
方法:采用脂多糖(LPS)(3 mg/kg)诱导ICR小鼠1次，三十天每天烟熏(CS)诱导30 min，建立PIC模型。从第24天开始，小鼠灌胃给药剂量分别为3.5、7、14 g/kg，连续2周。采用咳嗽次数、咳嗽潜伏期、酶联免疫吸附试验(ELISA)和组织学分析等方法研究苏黄止咳胶囊对PIC小鼠的影响。采用定量聚合酶链反应(Q-PCR)和免疫印迹法检测芳香烃受体(AhR)-NF-E2相关因子2(Nrf2)通路相关mRNA和蛋白水平。采用超氧化物歧化酶(SOD)、谷胱甘肽(GSH)和总抗氧化能力(T-AOC)测定评价氧化应激。以A549细胞为实验材料，观察苏黄止咳胶囊在体外的改善作用。
结果:苏黄止咳胶囊可有效减少PIC小鼠的咳嗽次数，延长咳嗽潜伏期。通过降低炎症介质肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的表达水平，减轻气道炎症。此外，苏黄止咳胶囊在体外和体内剂量依赖性地激活AhR-Nrf2通路，诱导核易位。苏黄止咳胶囊可显著提高小鼠SOD、GSH、T-AOC水平。
结论:在本研究中，我们证实苏黄止咳胶囊通过激活AhR-Nrf2通路，从而缓解炎症反应和氧化应激，从而改善LPS和CS诱导的小鼠的PIC。
Suhuang antitussive capsule ameliorates post-infectious cough in mice through AhR-Nrf2 pathway
Liang RY, Tong XY, Dong ZK, et al.
Abstract
BACKGROUND:Suhuang antitussive capsule (SH capsule), a typical traditional Chinese medicines (TCMs) compound, is widely used for the treatment of post-infectious cough (PIC) in the clinic. Our previous studies have demonstrated that SH capsule possesses significant ameliorative effects on cough variant asthma (CVA), sputum obstruction and airway remodeling.
OBJECTIVE:This study is designed to investigate the ameliorative effects and potential mechanisms of SH capsule on PIC in mice.
METHODS:To establish the PIC model, ICR mice were induced by lipopolysaccharide (LPS) (3 mg/kg) once, followed by cigarettes smoke (CS) exposure for 30 min per day for 30 days. Mice were intragastrically administrated with SH capsule at the doses of 3.5, 7, 14 g/kg each day for 2 weeks since the 24th day. The number of coughs, coughs latencies, enzyme-linked immunosorbent assay (ELISA) and histological analysis were used to investigate the effects of SH capsule on PIC mice. Quantitative-polymerase chain reaction (Q-PCR) and western blotting were conducted to evaluate the levels of mRNA and proteins associated with Aryl hydrocarbon receptor (AhR)–NF–E2-related factor 2 (Nrf2) pathway. Superoxide dismutase (SOD), glutathione (GSH) and total antioxidant capacity (T-AOC) assays were performed to evaluate the oxidative stress. A549 cells were used to investigate the ameliorative effects of SH capsule in vitro.
RESULTs:SH capsule effectively diminished the number of coughs and extended coughs latencies in PIC mice. The airway inflammation was alleviated by decreasing the expression levels of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Moreover, SH capsule dosedependently activated AhR-Nrf2 pathway and induced the nuclear translocation in vitro and in vivo. Besides, SH capsule significantly increased the levels of SOD, GSH and T-AOC in mice.
CONCLUSIONS:In the present study, we demonstrated that SH capsule ameliorated PIC in mice induced by LPS and CS via activation of AhR-Nrf2 pathway and consequent alleviation of inflammatory responses and oxidative stress.
背景:苏黄止咳胶囊(SH capsule)是典型的中药复方，临床上广泛用于治疗感染后咳嗽(PIC)。我们前期研究表明，SH胶囊对咳嗽变异性哮喘(CVA)、痰梗阻、气道重塑均有显著的改善作用。
目的:本研究旨在探讨苏黄止咳胶囊对小鼠PIC的改善作用及其可能机制。
方法:采用脂多糖(LPS)(3 mg/kg)诱导ICR小鼠1次，三十天每天烟熏(CS)诱导30 min，建立PIC模型。从第24天开始，小鼠灌胃给药剂量分别为3.5、7、14 g/kg，连续2周。采用咳嗽次数、咳嗽潜伏期、酶联免疫吸附试验(ELISA)和组织学分析等方法研究苏黄止咳胶囊对PIC小鼠的影响。采用定量聚合酶链反应(Q-PCR)和免疫印迹法检测芳香烃受体(AhR)-NF-E2相关因子2(Nrf2)通路相关mRNA和蛋白水平。采用超氧化物歧化酶(SOD)、谷胱甘肽(GSH)和总抗氧化能力(T-AOC)测定评价氧化应激。以A549细胞为实验材料，观察苏黄止咳胶囊在体外的改善作用。
结果:苏黄止咳胶囊可有效减少PIC小鼠的咳嗽次数，延长咳嗽潜伏期。通过降低炎症介质肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的表达水平，减轻气道炎症。此外，苏黄止咳胶囊在体外和体内剂量依赖性地激活AhR-Nrf2通路，诱导核易位。苏黄止咳胶囊可显著提高小鼠SOD、GSH、T-AOC水平。
结论:在本研究中，我们证实苏黄止咳胶囊通过激活AhR-Nrf2通路，从而缓解炎症反应和氧化应激，从而改善LPS和CS诱导的小鼠的PIC。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Journal of Ethnopharmacology, 2022, 283.）
（Journal of Ethnopharmacology, 2022, 283.）
Suhuang antitussive capsule ameliorates post-infectious cough in mice through AhR-Nrf2 pathway
Liang RY, Tong XY, Dong ZK, et al.
Abstract
BACKGROUND:Suhuang antitussive capsule (SH capsule), a typical traditional Chinese medicines (TCMs) compound, is widely used for the treatment of post-infectious cough (PIC) in the clinic. Our previous studies have demonstrated that SH capsule possesses significant ameliorative effects on cough variant asthma (CVA), sputum obstruction and airway remodeling.
OBJECTIVE:This study is designed to investigate the ameliorative effects and potential mechanisms of SH capsule on PIC in mice.
METHODS:To establish the PIC model, ICR mice were induced by lipopolysaccharide (LPS) (3 mg/kg) once, followed by cigarettes smoke (CS) exposure for 30 min per day for 30 days. Mice were intragastrically administrated with SH capsule at the doses of 3.5, 7, 14 g/kg each day for 2 weeks since the 24th day. The number of coughs, coughs latencies, enzyme-linked immunosorbent assay (ELISA) and histological analysis were used to investigate the effects of SH capsule on PIC mice. Quantitative-polymerase chain reaction (Q-PCR) and western blotting were conducted to evaluate the levels of mRNA and proteins associated with Aryl hydrocarbon receptor (AhR)–NF–E2-related factor 2 (Nrf2) pathway. Superoxide dismutase (SOD), glutathione (GSH) and total antioxidant capacity (T-AOC) assays were performed to evaluate the oxidative stress. A549 cells were used to investigate the ameliorative effects of SH capsule in vitro.
RESULTs:SH capsule effectively diminished the number of coughs and extended coughs latencies in PIC mice. The airway inflammation was alleviated by decreasing the expression levels of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Moreover, SH capsule dosedependently activated AhR-Nrf2 pathway and induced the nuclear translocation in vitro and in vivo. Besides, SH capsule significantly increased the levels of SOD, GSH and T-AOC in mice.
CONCLUSIONS:In the present study, we demonstrated that SH capsule ameliorated PIC in mice induced by LPS and CS via activation of AhR-Nrf2 pathway and consequent alleviation of inflammatory responses and oxidative stress.
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