Ameliorating Effect of Yifei Tongluo Prescription on Bleomycin-induced Pulmonary Fibrosis in Rats via Regulating NLRP3/Caspase-1/GSDMD Signaling Pathway and Epithelial-mesenchymal Transition
10.13422/j.cnki.syfjx.20250940
- VernacularTitle:益肺通络方调控NLRP3/Caspase-1/GSDMD信号通路及上皮-间充质转化对博来霉素诱导大鼠肺纤维化的改善作用
- Author:
Bowen ZHOU
1
;
Zefeng LI
2
;
Xian MA
1
;
Xuannian LI
1
;
Jingwen WANG
3
;
Fei XU
4
;
Huaman LIU
4
;
Xinhua JIA
4
Author Information
1. Shandong University of Traditional Chinese Medicine，Jinan 250355，China
2. Linshu County People's Hospital，Linyi 276700，China
3. Qingdao Hospital of Traditional Chinese Medicine，Qingdao 266033，China
4. Affiliated Hospital of Shandong University of Traditional Chinese Medicine，Jinan 250014，China
- Publication Type:Journal Article
- Keywords:
Yifei Tongluo prescription;
idiopathic pulmonary fibrosis;
NOD-like receptor protein 3 （NLRP3）;
epithelial-mesenchymal transition;
pyroptosis
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(1):150-159
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo observe the effects of Yifei Tongluo prescription on the NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pathway and epithelial-mesenchymal transition （EMT） in rats with pulmonary fibrosis. MethodsTracheal instillation of bleomycin was conducted to establish a rat model of pulmonary fibrosis. Thirty Sprague-Dawley （SD） rats were randomly divided into a blank group， a model group， a prednisone acetate group （1.17 mg·kg-1）， and low- and high-dose Yifei Tongluo prescription groups （10.62 and 21.24 g·kg-1， respectively）. Administration started on the 7th day after modeling， once a day for 28 consecutive days. The lung coefficient of each group was calculated. The pathological changes of lung tissues in each group were observed by hematoxylin-eosin （HE） staining and Masson staining. The expression of α-smooth muscle actin （α-SMA） and vimentin in rat lung tissues was detected by immunohistochemistry. The expression of NLRP3 inflammasome， E-cadherin （E-cad）， and typeⅠ collagen （ColⅠ） in lung tissues was detected by immunofluorescence. The content of hydroxyproline （HYP）， tumor necrosis factor （TNF）-α， interleukin （IL）-18， and IL-1β in rat serum was detected by enzyme-linked immunosorbent assay （ELISA）. The mRNA expression levels of NLRP3， apoptosis-associated speck-like protein containing a CARD （ASC）， IL-1β， and transforming growth factor （TGF）-β1 in rat lung tissues were determined by real-time quantitative polymerase chain reaction （Real-time PCR）. The protein expression levels of NLRP3， GSDMD， ASC， and Caspase-1 in rat lung tissues were determined by Western blot. ResultsCompared with the blank group， the model group exhibited a significantly increased lung coefficient （P<0.01） and significantly increased range of pulmonary interstitial inflammation and collagen deposition. In addition， the levels of α-SMA， Vimentin， E-cad， and ColⅠ in lung tissues were significantly increased （P<0.01）. The levels of fibrosis- and inflammation-related factors HYP， TNF-α， IL-18， and IL-1β in serum were significantly upregulated （P<0.01）. The levels of factors related to the activation of NLRP3 inflammasome in lung tissues， including NLRP3， GSDMD， ASC， Caspase-1， IL-1β， and TGF-β1， were significantly upregulated （P<0.01）. Compared with the model group， the Yifei Tongluo prescription groups showed improved lung coefficients. Additionally， the extent of lung inflammation and collagen deposition was significantly reduced. The expression of α-SMA， Vimentin， E-cad， and ColⅠ in lung tissue was significantly decreased （P<0.01）. The levels of HYP， TNF-α， IL-18， and IL-1β in serum were significantly reduced （P<0.01）. The expression levels of NLRP3， GSDMD， ASC， Caspase-1， IL-1β， and TGF-β1 in lung tissue were also significantly decreased （P<0.01）. ConclusionYifei Tongluo prescription can regulate the NLRP3/Caspase-1/GSDMD pathway， down-regulate release of pro-inflammatory and pro-fibrotic cytokines， alleviate NLRP3 inflammasome-mediated pyroptosis and EMT， and thereby improve pulmonary fibrosis in rats.
