一种中药配方通过下调 p65、JNK 和 p38 抑制炎症反应来改善 COPD。
A chinese herbal formula ameliorates COPD by inhibiting the inflammatory response via downregulation of p65, JNK, and p38.
机构信息
Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China; Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China; Department of Respiratory Diseases, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, China.
Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China; Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China; Department of Respiratory Diseases, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, China.
出版信息
Phytomedicine. 2021 Mar;83:153475. doi: 10.1016/j.phymed.2021.153475. Epub 2021 Jan 20.
BACKGROUND
Bufei Yishen formula (BYF), a traditional Chinese medicine (TCM), is an effective therapeutic strategy for patients with chronic obstructive pulmonary disease (COPD).
PURPOSE
To evaluate the efficacy of BYF and investigate its therapeutic mechanisms.
METHODS
A total of 134 patients completed the study: 68 patients treated by BYF combined with conventional Western medicine in the trial group; and 66 patients treated using conventional Western medicine in the control group. The efficacy of BYF was evaluated by a subgroup analysis of data obtained from a four-center, open-label, randomized controlled trial of comprehensive TCM interventions. A rat model of COPD was treated with the key active molecules (KAM) of BYF for 8 weeks. An in vitro model of COPD was also treated with KAM.
RESULTS
Patients treated with BYF had reduced frequency of acute exacerbation of COPD (p < 0.001) and duration (p = 0.028), dyspnea scale (p = 0.007), 6-min walking distance (p = 0.048). There were no differences observed in forced vital capacity in one second (FVC), forced expiratory volume in one second (FEV1), and FEV1 percentage of the predicted value (FEV1%). The five KAM of BYF (KAM-BYF) improved lung function, including tidal volume, minute ventilation, peak expiratory flow, FVC, FEV0.1, and FEV0.3, and pathological changes in COPD rats. Treatment with KAM-BYF markedly decreased the levels of interleukin 6 (IL6), tumor necrosis factor-α (TNF-α), matrix metalloproteinase 9 (MMP9), and MMP12 in serum and bronchial alveolar lavage fluid. In airway epithelial cells, KAM-BYF decreased the levels of TNF-α-induced IL8 and IL6. Finally, we discovered that the anti-inflammatory effects of KAM-BYF in COPD rats and BEAS-2Bs were mediated through inhibition of nuclear factor-kappaB (NF-κB) p65, c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase signaling.
CONCLUSIONS
BYF exerts beneficial effects in patients with COPD via inhibition of inflammation.
背景
补肺益肾方（BYF）是一种中药方剂，对慢性阻塞性肺疾病（COPD）患者具有显著疗效。
目的
评估 BYF 的疗效并探讨其作用机制。
方法
共有 134 例患者完成了研究：试验组 68 例患者采用补肺益肾方联合常规西药治疗；对照组 66 例患者仅采用常规西药治疗。通过对四项中医综合干预随机对照试验的中心数据进行亚组分析，评估补肺益肾方的疗效。将补肺益肾方的关键活性分子（KAM）用于 COPD 大鼠模型治疗 8 周，并建立 COPD 体外模型，同时使用 KAM 进行治疗。
结果
与对照组相比，补肺益肾方治疗组 COPD 急性加重的频率（p<0.001）和持续时间（p=0.028）、呼吸困难评分（p=0.007）、6 分钟步行距离（p=0.048）均显著降低。一秒用力呼气容积（FEV1）、FEV1 占预计值的百分比（FEV1%）等肺功能指标在两组间无差异。5 种补肺益肾方的关键活性分子（KAM-BYF）改善了 COPD 大鼠的肺功能，包括潮气量、分钟通气量、呼气峰流速、用力肺活量、FEV0.1 和 FEV0.3，同时减轻了 COPD 大鼠的肺部病理改变。KAM-BYF 治疗显著降低了血清和支气管肺泡灌洗液中白细胞介素 6（IL6）、肿瘤坏死因子-α（TNF-α）、基质金属蛋白酶 9（MMP9）和 MMP12 的水平。在气道上皮细胞中，KAM-BYF 降低了 TNF-α诱导的 IL8 和 IL6 水平。最后，我们发现 KAM-BYF 通过抑制核因子-κB（NF-κB）p65、c-Jun NH2-末端激酶（JNK）和 p38 丝裂原活化蛋白激酶信号通路，发挥对 COPD 大鼠和 BEAS-2B 细胞的抗炎作用。
结论
补肺益肾方通过抑制炎症反应对 COPD 患者具有有益的疗效。
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