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基于网络药理学和动物模型探讨金水六君煎联合巴戟天丸对慢性阻塞性肺疾病所致肌肉萎缩中Nrf2/HO-1通路的调控作用

Regulation of the Nrf2/HO-1 pathway in chronic obstructive pulmonary disease-induced muscle atrophy using Jinshui Liujian decoction and Bajitian pills: insights from network pharmacology and animal models.

作者信息

Lin Bai-Yang, Bai Li, Wang Sheng-Long

机构信息

Department of Respiratory, Shanxi Provincial People's Hospital, Taiyuan, 030001, China.

Department of Respiratory, Shanxi Provincial Integrated TCM and WM Hospital, The Third Clinical College of Shanxi University of Chinese Medicine, NO.13 of Fudong Road, Xinghualing District, Taiyuan, 030001, China.

出版信息

Hereditas. 2025 Apr 21;162(1):66. doi: 10.1186/s41065-025-00432-5.

DOI:10.1186/s41065-025-00432-5
PMID:40259353
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12012937/
Abstract

OBJECTIVE

This study aimed to investigate the therapeutic effects of the combination of modified Jinshui Liujian decoction and Bajitian pills (TCM) on chronic obstructive pulmonary disease (COPD)-induced muscle atrophy using network pharmacology and animal model experiments.

METHODS

Network pharmacology technique has been employed to analyze the potential targets of TCM on treating COPD. In vivo, COPD mice model was induced by lipopolysaccharide (LPS) combined with smoke treatment. To comparing the protective effects of TCM on this disease, these parameters including general condition, serum inflammatory factors, protein expression levels, gene copies, and histopathological changes in the lungs and gastrocnemius muscle mass have been further assessed in mouse in different groups.

RESULTS

Network pharmacology analysis identified 203 intersecting targets, primarily associated with apoptosis, phosphorylation, and inflammatory response. Animal experimental demonstrated that TCM could significantly improve the decreased skeletal muscle mass (p < 0.001), abnormal histopathologic morphology, decreased superoxide dismutase (SOD, p < 0.05), increased levels of serum malondialdehyde (MDA, p < 0.001) and tumor necrosis factor-α (TNF-α, p < 0.001) as compared to model group. Further mechanism exploration showed that a significant increase on the gene and proteins levels of nuclear factor erythroid 2-related factor 2 (NRF2, p < 0.05) and heme oxygenase-1 (HO-1, p < 0.05) have been observed in TCM-treated animals compared with that of in model animals. Interestingly, some indicators (serum MDA/SOD/TNF-α, RNA and protein levels of NRF2 and HO-1) showed more positive changes in TCM combined with western medicine (TCM-WN) - treated animals compared with that of TCM-treated animals.

CONCLUSION

Modified Jinshui Liujian decoction and Bajitian pills effectively mitigate muscle atrophy associated with COPD by modulating the Nrf2/HO-1 pathway through multi-target mechanisms. The combined TCM and WM therapy demonstrates enhanced therapeutic efficacy compared to monotherapy.

摘要

目的

本研究旨在通过网络药理学和动物模型实验,探讨加味金水六君煎联合巴戟天丸对慢性阻塞性肺疾病(COPD)所致肌肉萎缩的治疗作用。

方法

采用网络药理学技术分析中药治疗COPD的潜在靶点。在体内,通过脂多糖(LPS)联合烟熏处理诱导建立COPD小鼠模型。为比较中药对该疾病的保护作用,进一步评估了不同组小鼠的一般状况、血清炎症因子、蛋白表达水平、基因拷贝数以及肺和腓肠肌质量的组织病理学变化等参数。

结果

网络药理学分析确定了203个交集靶点,主要与细胞凋亡、磷酸化和炎症反应相关。动物实验表明,与模型组相比,中药可显著改善骨骼肌质量下降(p < 0.001)、异常组织病理学形态、超氧化物歧化酶降低(SOD,p < 0.05)、血清丙二醛水平升高(MDA,p < 0.001)和肿瘤坏死因子-α升高(TNF-α,p < 0.001)。进一步的机制探索表明,与模型动物相比,中药治疗的动物中核因子红细胞2相关因子2(NRF2,p < 0.05)和血红素加氧酶-1(HO-1,p < 0.05)的基因和蛋白水平显著升高。有趣的是,与中药治疗的动物相比,中西医结合(TCM-WN)治疗的动物中一些指标(血清MDA/SOD/TNF-α、NRF2和HO-1的RNA和蛋白水平)显示出更积极的变化。

结论

加味金水六君煎和巴戟天丸通过多靶点机制调节Nrf2/HO-1通路,有效减轻与COPD相关的肌肉萎缩。中西医结合疗法比单一疗法显示出更强的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f474/12012937/e9143475af93/41065_2025_432_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f474/12012937/488996f36921/41065_2025_432_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f474/12012937/3ad0534d172a/41065_2025_432_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f474/12012937/e9143475af93/41065_2025_432_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f474/12012937/488996f36921/41065_2025_432_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f474/12012937/f8adc354df46/41065_2025_432_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f474/12012937/222f5169b0a4/41065_2025_432_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f474/12012937/3ad0534d172a/41065_2025_432_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f474/12012937/e9143475af93/41065_2025_432_Fig5_HTML.jpg

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