Luotong Xianrong Yin Inhibits Pulmonary Injury in Idiopathic Pulmonary Fibrosis Rats by Regulating STAT3/HIF-1α-mediated Glycolysis
10.13422/j.cnki.syfjx.20251636
- VernacularTitle:络通纤溶饮抑制STAT3/HIF-1α介导的糖酵解改善特发性肺纤维化大鼠肺损伤
- Author:
Dongna LI
1
;
Hao WANG
1
;
Chaoyi FANG
1
;
Jiepeng WANG
1
Author Information
1. Hebei University of Chinese Medicine， Shijiazhuang 050200， China
- Publication Type:Journal Article
- Keywords:
idiopathic pulmonary fibrosis;
Luotong Xianrong Yin;
glycolysis;
signal transducer and activator of transcription 3 （STAT3）/hypoxia-inducible factor-1α （HIF-1α） signaling pathway;
pulmonary injury
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(4):118-125
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the characteristics and potential mechanisms of Luotong Xianrong Yin （LTXRY） in improving lung injury in rats with idiopathic pulmonary fibrosis （IPF） by regulating glycolysis. MethodsForty specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a sham-operated group （10 mL·kg-1）， model group （10 mL·kg-1）， LTXRY group （15.18 g·kg-1）， and nintedanib group （0.1 g·kg-1）， with 10 rats in each group. The IPF rat model was established by intratracheal instillation of bleomycin. After 28 days of gavage intervention， pulmonary function was assessed. Lung pathological changes were observed by hematoxylin-eosin （HE） and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6， in lung tissue. Chemiluminescence assays were employed to detect lactate content and lactate dehydrogenase activity in lung tissue. Western blot was used to measure the protein expression of transforming growth factor-β1 （TGF-β1）， CollagenⅠ and CollagenⅢ to evaluate collagen deposition， as well as hexokinase 2 （HK2）， pyruvate kinase M2 （PKM2）， and 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 3 （PFKFB3） to assess glycolysis levels. Network pharmacology was applied to analyze the potential targets and signaling pathways of LTXRY in IPF， and molecular docking was conducted to evaluate the binding energy between active components and potential targets. Western blot was further used to detect the expression of target- and pathway-related proteins. ResultsCompared with the sham-operated group， rats in the model group showed significantly increased main airway resistance （Rn） and respiratory system resistance （Rrs）， and significantly decreased respiratory system compliance （Crs）. Inflammatory infiltration and collagen deposition were observed in lung tissue， with significantly increased levels of TNF-α， IL-1β， and IL-6， as well as elevated protein expression of TGF-β1， CollagenⅠ and CollagenⅢ. Lactate content， lactate dehydrogenase activity， and the protein expression of HK2， PKM2， and PFKFB3 in lung tissue were significantly increased. Network pharmacology analysis indicated that signal transducer and activator of transcription 3 （STAT3） was a key target of LTXRY in IPF， and hypoxia-inducible factor-1 （HIF-1） was a critical signaling pathway. The expression levels of phosphorylated STAT3 （p-STAT3） and HIF-1α in lung tissue were significantly higher than those in the sham-operated group. Compared with the model group， rats in the LTXRY group showed significantly decreased Rn and Rrs and significantly increased Crs. Lung inflammatory infiltration and collagen deposition were markedly alleviated， with significantly reduced levels of TNF-α， IL-1β， and IL-6， and decreased protein expression of TGF-β1， CollagenⅠ and CollagenⅢ. Lactate content， lactate dehydrogenase activity， and the protein expression of HK2， PKM2， and PFKFB3 were significantly decreased， accompanied by markedly reduced expression of p-STAT3 and HIF-1α. ConclusionLTXRY alleviates lung tissue injury in IPF rats by regulating glycolysis mediated by the STAT3/HIF-1α signaling pathway.
