Effect and Mechanisms of Bushen Tongluo Prescription on Pulmonary Fibrosis via Inhibiting Macrophage Polarization Through Wnt3a/<italic style="font-style: italic">β</italic>-catenin Signaling Pathway

LIANG Yanxia; YU Xuelian; WANG Wenwen; LI Guangsen; XING Hongfei; FAN Maorong; YANG Bin

doi:10.13422/j.cnki.syfjx.20252207

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Effect and Mechanisms of Bushen Tongluo Prescription on Pulmonary Fibrosis via Inhibiting Macrophage Polarization Through Wnt3a/β-catenin Signaling Pathway

更新时间：2026-04-30

- Effect and Mechanisms of Bushen Tongluo Prescription on Pulmonary Fibrosis via Inhibiting Macrophage Polarization Through Wnt3a/β-catenin Signaling Pathway
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 32, Issue 11, Pages: 112-123(2026)
- 作者机构：
  
  1.中国中医科学院西苑医院，北京 100091
  2.烟台市牟平区中医医院，山东烟台 264000
  3.北京中医药大学，北京 100029
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20252207
  CLC： R289;R259;R285
- Received：10 August 2025，
  
  Revised：2025-10-20，
  
  Accepted：21 October 2025，
  
  Online First：22 October 2025，
  
  Published：05 June 2026
- 稿件说明：
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梁艳霞,于雪莲,王雯雯等.基于Wnt3a/β-catenin信号通路探讨补肾通络方抑制巨噬细胞极化缓解肺纤维化的作用及机制[J].中国实验方剂学杂志,2026,32(11):112-123.

LIANG Yanxia,YU Xuelian,WANG Wenwen,et al.Effect and Mechanisms of Bushen Tongluo Prescription on Pulmonary Fibrosis via Inhibiting Macrophage Polarization Through Wnt3a/β-catenin Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(11):112-123.
梁艳霞,于雪莲,王雯雯等.基于Wnt3a/β-catenin信号通路探讨补肾通络方抑制巨噬细胞极化缓解肺纤维化的作用及机制[J].中国实验方剂学杂志,2026,32(11):112-123. DOI： 10.13422/j.cnki.syfjx.20252207.

LIANG Yanxia,YU Xuelian,WANG Wenwen,et al.Effect and Mechanisms of Bushen Tongluo Prescription on Pulmonary Fibrosis via Inhibiting Macrophage Polarization Through Wnt3a/β-catenin Signaling Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2026,32(11):112-123. DOI： 10.13422/j.cnki.syfjx.20252207.

摘要

目的

探讨补肾通络方是否可通过调控Wnt3a/

-连环蛋白（

-catenin）信号通路抑制巨噬细胞极化，进而减少上皮细胞-间质细胞转化及细胞外基质过度沉积，以期阐明补肾通络方抗肺纤维化的作用机制，为临床治疗肺纤维化提供新的理论依据。

方法

将50只雄性SD大鼠随机分为空白组，模型组，吡非尼酮组，补肾通络方高、低剂量组。除空白组外，其余各组采用气管内注入博来霉素构建肺纤维化模型。造模后第28天进行干预，补肾通络方高、低剂量组分别予补肾通络方30.88、15.44 g·kg

-1

灌胃，吡非尼酮组予吡非尼酮胶囊110 mg·kg

-1

灌胃，空白组、模型组予等量生理盐水灌胃，每日1次，共治疗90 d。治疗结束后，酶联免疫吸附测定法（ELISA）检测各组大鼠支气管肺泡灌洗液（BALF）中转化生长因子-

（TGF-

）水平；比较大鼠肺组织形态变化及胶原容积分数；免疫组化法检测肺组织中E-钙黏蛋白（E-cadherin）、细胞角蛋白19（Cytokeratin 19）、

α-

平滑肌肌动蛋白（

-SMA）、细胞骨架蛋白（Vimentin）、Ⅰ型胶原（Col Ⅰ）、Ⅲ型胶原（Col Ⅲ）蛋白分布及表达；免疫荧光法检测肺组织中分化簇68/巨噬细胞唾液酸糖蛋白（CD68）、精氨酸酶-1（Arg-1）、诱导型一氧化氮合酶（iNOS）、Wnt3a、

-catenin的蛋白分布及表达；蛋白免疫印迹法检测肺组织中Wnt3a、

-catenin的蛋白表达；实时荧光定量聚合酶链式反应（Real-time PCR）检测肺组织中Wnt3a、

-catenin mRNA表达。

结果

与空白组比较，模型组大鼠气道壁、肺泡腔、间质组织内出现大量炎性细胞浸润，纤维组织增生明显；BALF中TGF-

水平显著升高；肺组织内E-cadherin、Cytokeratin 19蛋白表达下降，

-SMA、Vimentin、Wnt3a、

-catenin、Col Ⅰ、Col Ⅲ蛋白表达均升高；大鼠肺组织中CD68、Arg-1、iNOS、Wnt3a、

-catenin荧光阳性面积比率升高；大鼠肺组织中Wnt3a、

-catenin蛋白及mRNA表达均显著升高（

0.01）。与模型组比较，各治疗组均不同程度改善气道壁、肺泡腔、间质组织内炎性细胞浸润及纤维组织增生；降低BALF中TGF-

水平；升高肺组织中E-cad

herin、Cytokeratin 19蛋白表达，降低肺组织中

-SMA、Vimentin、Col Ⅰ、Col Ⅲ蛋白表达；降低肺组织中CD68、Arg-1、iNOS、Wnt3a、

-catenin荧光阳性面积比率；降低肺组织中Wnt3a、

-catenin蛋白及mRNA表达（

0.05，

0.01）。

结论

补肾通络方能够通过抑制上皮细胞-间质细胞转化、减少细胞外基质过度沉积，从而改善博来霉素所致的大鼠肺纤维化，其机制或与抑制Wnt3a/

-catenin信号通路及其介导的巨噬细胞极化有关。

Abstract

Objective

This study aimed to investigate whether Bushen Tongluo prescription inhibits macrophage polarization by regulating the Wnt3a/

-catenin signaling pathway， thereby reducing epithelial-mesenchymal transition and excessive extracellular matrix deposition， in order to elucidate the anti-pulmonary fibrosis mechanisms of Bushen Tongluo prescription and provide a new theoretical basis for the clinical treatment of pulmonary fibrosis.

Methods

Fifty male Sprague-Dawley （SD） rats were randomly divided into a blank group， model group， pirfenidone group， and high- and low-dose Bushen Tongluo prescription groups. Except for the blank group， the pulmonary fibrosis model was established by intratracheal instillation of bleomycin. Intervention was initiated on day 28 after modeling. The high- and low-dose Bushen Tongluo prescription groups were administered Bushen Tongluo prescription at doses of 30.88， 15.44 g·kg

-1

， respectively， by intragastric gavage. The pirfenidone group was administered pirfenidone capsules at 110 mg·kg

-1

by intragastric gavage. The blank and model groups were given an equal volume of normal saline by gavage， once daily for 90 days. After treatment， the level of transforming growth factor-

（TGF-

） in bronchoalveolar lavage fluid （BALF） was detected by enzyme-linked immunosorbent assay （ELISA）. Morphological changes in lung tissue and the collagen volume fraction were compared. The protein d

istribution and expression of E-cadherin， cytokeratin 19，

-smooth muscle actin （

-SMA）， vimentin， collagen type Ⅰ （Col Ⅰ）， and collagen type Ⅲ （Col Ⅲ） in lung tissue were detected by immunohistochemistry. The protein distribution and expression of CD68， arginase-1 （Arg-1）， inducible nitric oxide synthase （iNOS）， Wnt3a， and

-catenin in lung tissue were detected by immunofluorescence. The protein expression of Wnt3a and

-catenin in lung tissue was detected by Western blot， and the mRNA expression of Wnt3a and

-catenin was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）.

Results

Compared with the blank group， a large number of inflammatory cells infiltrated the airway walls， alveolar spaces， and interstitial tissue in the model group， with obvious fibrous tissue hyperplasia. The level of TGF-

in BALF was significantly increased. The protein expression of E-cadherin and cytokeratin 19 in lung tissue was decreased， whereas the protein expression of

-SMA， Vimentin， Wnt3a，

-catenin， Col Ⅰ， and Col Ⅲ was increased. The fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and

-catenin in lung tissue were increased. The protein and mRNA expression levels of Wnt3a and

-catenin in lung tissue were significantly increased （

0.01）. Compared with the model group， all treatment groups showed varying degrees of improvement in inflammatory cell infiltration and fibrous tissue hyperplasia in the airway walls， alveolar spaces， and interstitial tissue， decreased TGF-

levels in BALF， increased protein expression of E-cadherin and cytokeratin 19 in lung tissue， decreased protein expression of

-SMA， Vimentin， Col Ⅰ， and Col Ⅲ， decreased fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， a

-catenin in lung tissue， and decreased protein and mRNA expression levels of Wnt3a and

-catenin in lung tissue （

0.05，

0.01）.

Conclusion

Bushen Tongluo prescription can improve bleomycin-induced pulmonary fibrosis in rats by inhibiting epithelial-mesenchymal transition and reducing excessive extracellular matrix deposition. The mechanism may be related to inhibition of the Wnt3a/

-catenin signaling pathway and the macrophage polarization mediated by this pathway.

关键词

Keywords

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Effect and Mechanisms of Bushen Tongluo Prescription on Pulmonary Fibrosis via Inhibiting Macrophage Polarization Through Wnt3a/β-catenin Signaling Pathway

DOI：10.13422/j.cnki.syfjx.20252207

摘要

Abstract

关键词

Keywords

references