补肺益肾方 III 的有效成分配伍通过 Pkm2/Nrf2 通路抑制 COPD 模型大鼠的线粒体氧化损伤。

Effective-Component Compatibility of Bufei Yishen Formula III Suppresses Mitochondrial Oxidative Damage in COPD: Via Pkm2/Nrf2 Pathway.

机构信息

Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan Province and Education Ministry of People's Republic of China, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China.

School of Basic Medicine (Zhongjing School), Henan University of Chinese Medicine, Zhengzhou, People's Republic of China.

出版信息

Int J Chron Obstruct Pulmon Dis. 2024 Aug 24;19:1905-1920. doi: 10.2147/COPD.S468825. eCollection 2024.

DOI:10.2147/COPD.S468825

PMID:39206144

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11352541/

Abstract

PURPOSE

The main objective of this study was to explore the mechanism of effective component compatibility of Bufei Yishen formula III (ECC-BYF III) in inhibiting mitochondrial oxidative stress in a rat model of chronic obstructive pulmonary disease (COPD).

METHODS

A549 cells exposed to cigarette smoke extract (CSE) were used to establish a model of mitochondrial oxidative damage. The cells were treated with the plasmid encoding Pkm2 and the enzymes and proteins involved in oxidative stress and mitochondrial function were measured. A rat model of COPD was established using CS and bacteria. Two different treatments were established, ECC-BYF III (5.5 mg/kg/d) and N-acetylcysteine (54 mg/kg/day). Animals were tested for pulmonary function (Vt, PEF, FVC, FEV0.1s and Cdyn) after eight weeks of therapy and were sacrificed. Pulmonary H&E staining was performed, and the total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) content were measured. The mitochondrial function was also examined. Furthermore, the Pkm2/Nrf2 signaling pathway was evaluated.

RESULTS

Overexpression of Pkm2 dramatically ameliorated the CS-induced mitochondrial oxidative damage. Further studies indicated that ECC-BYF III significantly improved mitochondrial function and inhibited oxidative stress in the lung tissues of COPD rats. Moreover, it can upregulate mitochondrial respiratory chain enzyme activity. ECC-BYF III also decreased the MDA content and increased T-SOD, GSH-Px, and T-AOC expression to facilitate oxidative homeostasis. Finally, our results indicated that the Pkm2/Nrf2 pathway is regulated by ECC-BYF III in A549 cells and lung tissue.

CONCLUSION

These results indicate that ECC-BYF III exerts a strong effective therapeutic effect against cigarette smoke combined with bacteria-induced COPD in rats by activating the Pkm2/Nrf2 signaling pathway and restoring mitochondrial oxidative stress. Although more in vivo animal model research is needed to confirm these findings, this study contributes new data to support the conventional usage of ECC-BYF III.

摘要

目的

本研究的主要目的是探讨补肺益肾方 III（ECC-BYF III）有效成分配伍抑制慢性阻塞性肺疾病（COPD）大鼠模型线粒体氧化应激的机制。

方法

用香烟烟雾提取物（CSE）处理 A549 细胞建立线粒体氧化损伤模型。用编码 Pkm2 的质粒和参与氧化应激和线粒体功能的酶和蛋白处理细胞。用 CS 和细菌建立 COPD 大鼠模型。建立了两种不同的治疗方法，ECC-BYF III（5.5mg/kg/d）和 N-乙酰半胱氨酸（54mg/kg/天）。治疗 8 周后，对动物进行肺功能（Vt、PEF、FVC、FEV0.1s 和 Cdyn）测试，然后处死动物。进行肺组织 H&E 染色，并测量总超氧化物歧化酶（T-SOD）、谷胱甘肽过氧化物酶（GSH-Px）、总抗氧化能力（T-AOC）和丙二醛（MDA）含量。还检查了线粒体功能。此外，评估了 Pkm2/Nrf2 信号通路。

结果

过表达 Pkm2 可显著改善 CS 诱导的线粒体氧化损伤。进一步的研究表明，ECC-BYF III 可显著改善 COPD 大鼠的线粒体功能并抑制肺组织氧化应激，还能上调线粒体呼吸链酶的活性。ECC-BYF III 还降低 MDA 含量，增加 T-SOD、GSH-Px 和 T-AOC 的表达，以促进氧化平衡。最后，我们的结果表明，ECC-BYF III 通过调节 Pkm2/Nrf2 通路在 A549 细胞和肺组织中发挥作用。