Bu-Shen-Fang-Chuan formula attenuates cigarette smoke-induced inflammation by modulating the PI3K/Akt-Nrf2 and NF-κB signalling pathways
Bu-Shen-Fang-Chuan formula attenuates cigarette smoke-induced inflammation by modulating the PI3K/Akt-Nrf2 and NF-κB signalling pathways
复制标题
补肾防喘方通过调节 PI3K/Akt-Nrf2 和 NF-κB 信号通路减轻香烟烟雾引起的炎症
DOI：
10.1016/j.jep.2020.113095
复制
发表时间：
2020-10-28
影响因子：
5.4
通讯作者：
Wu, Jinfeng
中科院分区：
文献类型：
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作者：
Li, Qiuping;Wang, Guifang;Wu, Jinfeng
民族药理学相关性：慢性阻塞性肺疾病（COPD）是一种呼吸道炎症性疾病。与哮喘不同，慢性阻塞性肺病对糖皮质激素治疗不敏感；因此，寻找包括中药在内的替代药物来抑制炎症是非常重要的。补肾防喘方（BSFCF）是中国治疗慢性阻塞性肺病的常用方。然而，BSFCF在COPD治疗中的作用机制尚不清楚。研究目的：基于磷脂酰肌醇3激酶(PI3K)/蛋白激酶B (Akt)-核因子-红细胞2相关因子2 （Nrf2）和核因子- κ B信号通路，验证BSFCF对COPD的抗炎作用，探讨其抗炎作用的可能机制。材料与方法：建立慢性暴露于香烟烟雾（CS） 6个月的COPD大鼠模型。取支气管肺泡灌洗液（BALF）和血液检测炎症因子。采集肺样本，每个样本的一部分固定用于随后的H&E染色和免疫组织化学（IHC）分析。其余肺组织进行RNA测序分析和western blotting。结果：BSFCF可显著降低cs暴露大鼠肺部炎症浸润，降低BALF和血清中肿瘤坏死因子(TNF)- α和白细胞介素(IL)-6的浓度。此外，BSFCF可明显减弱CS引起的NF-kappa B活化和糖皮质激素受体（GR）下调。此外，BSFCF在CS应答中增加了PI3K/Akt-Nrf2信号的激活。结论：BSFCF可减轻cs诱导的COPD炎症，部分通过PI3K/Akt-Nrf2和NF-kappa B信号通路实现。
Ethnopharmacological relevance: Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory disease. Unlike asthma, COPD is insensitive to glucocorticoid treatment; thus, it is of great importance to find alternative medications, including Chinese medicine, to suppress inflammation. Bu-Shen-Fang-Chuan formula (BSFCF) is commonly used for the treatment of COPD in China. However, the mechanisms of BSFCF in COPD treatment are still unclear.Aim of the study: To verify the anti-inflammatory efficacy of BSFCF in COPD and to explore the possible mechanisms underlying its anti-inflammatory efficacy based on the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)-Nuclear factor erythroid 2-related factor 2 (Nrf2) and Nuclear factor (NF)-kappa B signalling pathways.Materials and methods: A rat model of COPD was established by chronic exposure to cigarette smoke (CS) for 6 months. Bronchoalveolar lavage fluid (BALF) and blood were obtained to detect inflammatory cytokines. Lung samples were harvested, and part of each sample was fixed for subsequent H&E staining and immunohistochemical (IHC) analysis. The remaining lung tissues were used for RNA sequencing analysis and western blotting.Results: BSFCF significantly reduced inflammatory infiltration in the lungs of CS-exposed rats and decreased the concentrations of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 in both the BALF and serum. Additionally, BSFCF evidently attenuated NF-kappa B activation and downregulation of glucocorticoid receptor (GR) caused by CS. Furthermore, BSFCF increased the activation of PI3K/Akt-Nrf2 signalling in response to CS.Conclusions: BSFCF attenuated CS-induced inflammation in COPD, which was partially achieved through the PI3K/Akt-Nrf2 and NF-kappa B signalling pathways.