法半夏通过巨噬细胞和成纤维细胞的Crosstalk减轻COPD损伤机制研究

doi:10.12092/j.issn.1009-2501.2026.05.002

中国临床药理学与治疗学 ›› 2026, Vol. 31 ›› Issue (5): 585-595.doi: 10.12092/j.issn.1009-2501.2026.05.002

法半夏通过巨噬细胞和成纤维细胞的Crosstalk减轻COPD损伤机制研究

魏宗烽(), 谭金龙, 孙梦涵, 朱乃亮, 翟莹莹, 陈琼, 毕晶晶, 梁利香(), 宋敏()

信阳农林学院药学院，信阳 464000，河南

收稿日期:2025-06-09 修回日期:2025-09-03 出版日期:2026-05-26 发布日期:2026-06-02
通讯作者: 梁利香,宋敏 E-mail:21968611@qq.com;916912572@qq.com;1797405679@qq.com
作者简介:魏宗烽，男，硕士，副教授，研究方向：中药学。E-mail：21968611@qq.com
基金资助:
国家自然科学基金青年项目（21702051）；河南省自然科学基金面上项目（232300420065）；河南省重点研发与推广专项（232102310364；252102311246）；河南省重大专项（241111311400）；河南省高校重点科研项目（24B3600014）；信阳农林学院青年基金项目（QN2023025；QN2023028）

Mechanism study of Processed Pinellia ternata alleviating COPD injury through macrophages and fibroblasts Crosstalk

Zongfeng WEI(), Jinlong TAN, Menghan SUN, Nailiang ZHU, Yingying ZHAI, Qiong CHEN, Jingjing BI, Lixiang LIANG(), Min SONG()

Collage of Pharmacy, Xinyang Agriculture and Forestry University, Xinyang 464000, Henan, China

Received:2025-06-09 Revised:2025-09-03 Online:2026-05-26 Published:2026-06-02
Contact: Lixiang LIANG,Min SONG E-mail:21968611@qq.com;916912572@qq.com;1797405679@qq.com

摘要/Abstract

摘要：

目的: 探讨法半夏治疗慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）的作用机制。方法: 将40只雄性C57BL/6J小鼠随机分为对照组（n=8）、模型组（n=12）、法半夏组（1.5 g/kg，n=12）和氨茶碱组（1 mg/kg，n=8）。采用烟熏联合脂多糖滴鼻法建立COPD小鼠模型。HE染色观察小鼠肺组织病理损伤，MASSON、MMP2和MMP9的免疫组化染色检测肺组织纤维化，α-SMA免疫组化染色检测肺组织成纤维细胞的转化，CD206和F4/80免疫组化染色检测肺组织M2巨噬细胞极化，qPCR检测TGF-β1和Arg-1基因表达，Western blot检测肺组织中Stat1、p-Stat1蛋白表达。此外，通过Transwell小室对巨噬细胞和成纤维细胞进行共培养，分为空白组、对照组、模型组、法半夏低、中、高剂量组（10、20、40 μg/mL），α-SMA免疫荧光检测成纤维细胞的转化。结果: 法半夏能明显减轻COPD损伤（P<0.01），抑制肺组织增生和纤维化（P<0.001），降低TGF-β1和Arg-1基因相对表达量（P<0.05），抑制成纤维细胞的转化（P<0.05），减少M2型巨噬细胞极化（P<0.05），增加p-Stat1/Stat1比率（P<0.05）。结论: 法半夏通过阻断巨噬细胞和成纤维细胞的Crosstalk改善COPD的纤维化进程，可能与法半夏激活Stat1通路抑制M2型巨噬细胞极化有关。

关键词: 法半夏, 慢性阻塞性肺疾病, 纤维化, Crosstalk

Abstract:

AIM: To explore the mechanism of Processed Pinellia ternata in treating chronic obstructive pulmonary disease (COPD). METHODS: Forty male C57BL/6J mice were randomly divided into control group (n=8), model group (n=12), Processed Pinellia ternata group (1.5 g/kg, n=12), and aminophylline group (1 mg/kg, n=8). COPD model was established using smoke inhalation combined with lipopolysaccharide nasal drops. HE staining was employed to observe pathological damage in lung tissue. Lung tissue fibrosis was detected by Masson, MMP2, and MMP9 staining. Fibroblast transformation was tested α-SMA staining. CD206 and F4/80 staining were used to evaluated M2 macrophages polarization. The expression of TGF-β1 and Arg-1 genes were checked though qPCR, the level of Stat1 and p-Stat1 proteins were measured by Western blotting. In addition, macrophages and fibroblasts were co-cultured by transwell chambers, the (cells) were divided into blank control group, normal control group, model group, and low-, medium-, high-dose Pinellia ternata group groups (10, 20, 40 μg/mL, respectively), the fibroblasts transformation was detected by α-SMA staining. RESULTS: Processed Pinellia ternata can significantly alleviate COPD injury (P<0.01), inhibit lung tissue proliferation and fibrosis (P<0.001), reduce the relative expression levels of TGF-β1 and Arg-1 genes (P<0.05), inhibit fibroblast transformation (P<0.05), reduce M2 macrophage polarization (P<0.05) and increase the p-Stat1/Stat1 ratio (P<0.05). CONCLUSION: Processed Pinellia ternata improves the fibrosis process in COPD by macrophages and fibroblasts crosstalk blocking, which may be related to suppressed M2 macrophage polarization and activated the Stat1 pathway.

Key words: Processed Pinellia ternata, chronic obstructive pulmonary disease (COPD), fibrosis, Crosstalk

中图分类号:

R965.2

魏宗烽, 谭金龙, 孙梦涵, 朱乃亮, 翟莹莹, 陈琼, 毕晶晶, 梁利香, 宋敏. 法半夏通过巨噬细胞和成纤维细胞的Crosstalk减轻COPD损伤机制研究[J]. 中国临床药理学与治疗学, 2026, 31(5): 585-595.

Zongfeng WEI, Jinlong TAN, Menghan SUN, Nailiang ZHU, Yingying ZHAI, Qiong CHEN, Jingjing BI, Lixiang LIANG, Min SONG. Mechanism study of Processed Pinellia ternata alleviating COPD injury through macrophages and fibroblasts Crosstalk[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(5): 585-595.

图/表 10

表 1

Table 1 Primer sequences

Gene	Forward primer	Reward primer
TGF-β1	ACTGGAGTTGTACGGCAGTG	GGGGCTGATCCCGTTGATTT
Arg-1	AGCACTGAGGAAAGCTGGTC	TACGTCTCGCAAGCCAATGT
GAPDH	ACAGCAACAGGGTGGTGGAC	TTTGAGGGTGCAGCGAACTT

图 1

Fig.1 The effect of Processed Pinellia ternata on COPD ($\bar x $±s, n≥8) A: lung tissues photos in groups; B: lung/body weight ratio analysis. ***P<0.001, compared with control group; ##P<0.01, compared with model group.

图 2

Fig.2 The effect of Processed Pinellia ternata on lung tissue injury ($\bar x $±s, n=3) A: HE staining of alveoli in each group; B: HE staining of bronchi in each group; C-F: statistical analysis of WT%, WA%, smooth muscle thickness and bronchial wall thickness. ****P<0.001, compared with control group; ###P<0.001, compared with model group.

图 3

Fig.3 The effect of Processed Pinellia ternata on pulmonary fibrosis ($\bar x $±s, n=3) A-B: Alveolar Masson staining and fibrosis analysis in each group; C-D: Bronchi Masson staining and fibrosis analysis in each group; ***P<0.001, compared with control group; ###P<0.001, compared with model group.

图 4

Fig.4 The effect of Processed Pinellia ternata on the expression of MMP2 and MMP9 ($\bar x $±s, n=3) A-D: Immunohistochemical staining and quantitative analysis of MMP2 in the alveoli and bronchi of lung tissue; E-H: Immunohistochemical staining and quantitative analysis in the alveoli and bronchi of lung tissue; ***P<0.001, compared with control group; ###P<0.001, compared with model group.

图 5

Fig.5 The effect of Processed Pinellia ternata on fibroblast transformation in COPD model ($\bar x $±s, n=3) A-B: α-SMA immunohistochemical staining and quantitative analysis of alveolar in each group; C-D: α-SMA immunohistochemical staining and quantitative analysis of bronchi in each group; **P<0.01, compared with control group; #P<0.05, ##P<0.01, compared with model group.

图 6

Fig.6 Effect of Processed Pinellia ternata on fibroblast transformation in co-culture model ($\bar x $±s, n=3) A: Co-culure model establishment; B-C: α-SMA immunofluorescence staining and quantitative analysis of each group; ***P<0.001, compared with control group; ###P<0.001, compared with model group.

图 7

Fig.7 The effect of Processed Pinellia ternata on the expression of TGF-β1 and Arg-1 ($\bar x $±s, n=3) A-B: TGF-β1 and Arg-1 genes expression and quantitative analysis in the lung tissues. *P<0.05, ***P<0.001, compared with control group; #P<0.05, ##P<0.01, compared with model group.

图 8

Fig.8 The effect of Processed Pinellia ternata on M2 macrophages polarization ($\bar x $±s, n=3) A: F4/80 immunohistochemical staining in lung tissue; B: CD206 immunohistochemical staining in lung tissue; C: Quantitative analysis of CD206/F4/80 ratio. **P<0.01, compared with control group; #P<0.05, compared with model group.

图 9

Fig.9 The effect of Processed Pinellia ternata on the Stat1 signaling pathway ($\bar x $±s, n=3) A-B: expression levels and quantitative analysis of p-Stat1, Stat1 and β-actin in lung tissues. *P<0.05, compared with control group; #P<0.05, compared with model group.

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法半夏通过巨噬细胞和成纤维细胞的Crosstalk减轻COPD损伤机制研究

Mechanism study of Processed Pinellia ternata alleviating COPD injury through macrophages and fibroblasts Crosstalk

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