通过神气花丹煎剂激活过氧化物酶体增殖物激活受体 Gamma 介导的活化蛋白激酶/叉头转录因子 O3a 信号通路改善慢性阻塞性肺病大鼠的氧化应激反应

IF 2.1 4区 医学 Q3 RESPIRATORY SYSTEM Canadian respiratory journal Pub Date : 2024-07-02 eCollection Date: 2024-01-01 DOI:10.1155/2024/5647813
Jingjing Chen, Wenxiao Qiao, Xiaoming Xue, Dian Li, Ye Zhang, Di Xie, Jinyun Wang, Yaoqin Sun, Shuo Yang, Zhuomin Yang
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引用次数: 0

摘要

背景:慢性阻塞性肺疾病(COPD)是一种常见的呼吸系统疾病。目前,尚无特效的治疗策略,因此,寻找新的治疗方法至关重要。临床上,神气化瘀汤是治疗慢性阻塞性肺疾病的传统中药方剂,但其治疗作用机制尚待明确:方法:通过吸烟和气管注射 LPS 法复制 COPD 大鼠模型。对照组和 SQHT 组分别灌胃地塞米松和 SQHT 治疗。治疗后,用酶联免疫吸附试验(ELISA)检测超氧化物歧化酶(SOD)血清水平、总抗氧化能力(TAOC)、脂质过氧化和丙二醛(MDA)。使用逆转录酶定量聚合酶链反应(RT-qPCR)和 Western 印迹法检测活化蛋白激酶α(AMPK-α)、叉头转录因子 O3a(FOXO3a)、锰 SOD(MnSOD)和过氧化物酶体增殖激活受体γ(PPARγ)。测定微核糖核酸和蛋白质的表达水平,并用苏木精和伊红染色观察肺组织的病理变化:结果:病理研究结果表明,SQHT 通过增强肺泡融合和减轻肺气肿对慢性阻塞性肺疾病的治疗有显著影响。酶联免疫吸附试验结果表明,SQHT 可降低血液中 MDA 和过氧化脂质的水平,提高 SOD 和 TAOC 的水平,从而减轻氧化应激。在慢性阻塞性肺病大鼠的肺组织中,大剂量 SQHT 干预可显著增加 AMPK 蛋白表达、AMPK-α、FOXO3a、MnSOD 和 PPARγ,表明 SQHT 可通过激活 PPARγ 介导的 AMPK/FOXO3a 信号通路来减轻氧化应激。使用 RT-qPCR 也得到了类似的结果:结论:SQHT 可有效治疗慢性阻塞性肺疾病。其作用机制可能与激活 PPARγ 介导的 AMPK/FOXO3a 信号通路以改善肺组织中的氧化应激有关。
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Amelioration of Oxidative Stress in Rats with Chronic Obstructive Pulmonary Disease through Shenqi Huatan Decoction Activation of Peroxisome Proliferator-Activated Receptor Gamma-Mediated Activated Protein Kinase/Forkhead Transcription Factor O3a Signaling Pathway.

Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease. Currently, no specific treatment strategy has been established; therefore, finding new treatment methods is essential. Clinically, Shenqi Huatan Decoction (SQHT) is a traditional Chinese medicinal formula for COPD treatment; however, its mechanism of action in treatment needs to be clarified.

Methods: The COPD rat model was replicated by cigarette smoking and tracheal injection using the LPS method. The control group and the SQHT groups were treated with dexamethasone and SQHT by gavage, respectively. After treatment, superoxide dismutase (SOD) serum levels, total antioxidant capacity (TAOC), lipid peroxidation, and malondialdehyde (MDA) were detected by enzyme-linked immunosorbent assay (ELISA). Activated protein kinase alpha (AMPK-α), forkhead transcription factor O3a (FOXO3a), manganese SOD (MnSOD), and peroxisome proliferator-activated receptor gamma (PPARγ) were detected using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and Western blot. Microribonucleic acid and protein expression levels were measured, and pathological changes in lung tissue were observed using hematoxylin and eosin staining.

Results: The pathological findings suggested that SQHT substantially affects COPD treatment by enhancing alveolar fusion and reducing emphysema. ELISA results showed that SQHT could lower the blood levels of MDA and lipid peroxide and raise SOD and TAOC levels, suggesting that it could lessen oxidative stress. In the lung tissue of rats with COPD, large doses of SQHT intervention dramatically increased AMPK protein expression, AMPK-α, FOXO3a, MnSOD, and PPARγ, indicating that SQHT may reduce oxidative stress by activating the PPARγ-mediated AMPK/FOXO3a signaling pathway. Similar results were obtained using RT-qPCR.

Conclusion: SQHT is effective for COPD treatment. The mechanism of action may be related to the activation of the PPARγ-mediated AMPK/FOXO3a signaling pathway to improve oxidative stress in lung tissue.

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来源期刊
Canadian respiratory journal
Canadian respiratory journal 医学-呼吸系统
CiteScore
4.20
自引率
0.00%
发文量
61
审稿时长
6-12 weeks
期刊介绍: Canadian Respiratory Journal is a peer-reviewed, Open Access journal that aims to provide a multidisciplinary forum for research in all areas of respiratory medicine. The journal publishes original research articles, review articles, and clinical studies related to asthma, allergy, COPD, non-invasive ventilation, therapeutic intervention, lung cancer, airway and lung infections, as well as any other respiratory diseases.
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