Exploring Mechanism of Polygoni Cuspidati Rhizoma et Radix in Treating Respiratory Syncytial Virus Infection Based on Pulmonary Surfactant Lipid Homeostasis
10.13422/j.cnki.syfjx.20251364
- VernacularTitle:基于肺表面活性脂质稳态探究虎杖治疗呼吸道合胞病毒感染的作用机制
- Author:
Xiaorong WANG
1
;
Keyu TAO
2
;
Jianjian JI
2
;
Yingmei DONG
2
Author Information
1. Affiliated Hospital of Nanjing University of Chinese Medicine，Jiangsu Province Hospital of Chinese Medicine，Nanjing 210029，China
2. Jiangsu Key Laboratory of Children's Health and Chinese Medicine，Nanjing University of Chinese Medicine，Nanjing 210023，China
- Publication Type:Journal Article
- Keywords:
respiratory syncytial virus（RSV）;
Polygoni Cuspidati Rhizoma et Radix;
pulmonary surfactant lipids;
lipidomics;
metabolomics;
viral pneumonia
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(21):102-108
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the efficacy and mechanism of Polygoni Cuspidati Rhizoma et Radix （Huzhang） in treating respiratory syncytial virus（RSV） infection by regulating pulmonary surfactant lipid homeostasis through lipidomics. MethodsSixty BALB/c mice were randomly divided into the blank group， model group， positive group（ribavirin group， 46 mg·kg-1）， and low- and high-dose Huzhang groups（0.75， 2.25 g·kg-1）， with 12 mice in each group. Except for the blank group， all other groups were infected with RSV via intranasal instillation. The drug intervention groups were given corresponding doses of drug by gavage for 3 consecutive days， while normal saline was used in the blank and model groups. Hematoxylin-eosin（HE） staining was used to observe pathological changes in mouse lung tissue. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was employed to detect viral loads［RSV-nucleoprotein（N） and RSV-glycoprotein（G） mRNA］ and inflammatory factor levels［interleukin（IL）-1β and tumor necrosis factor（TNF）-α mRNA］ in the lung tissue. Mouse bronchoalveolar lavage fluid was collected to detect the levels of pulmonary surfactant lipids through ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap-MS）， followed by principal component analysis and differential lipid identification. ResultsCompared with the blank group， the model group exhibited extensive inflammatory cell infiltration， congestion， and tissue damage in the lungs， and the pathological score and lung index of lung tissue significantly increased（P<0.01）， along with significantly elevated mRNA expressions of RSV-N， RSV-G， IL-1β， and TNF-α（P<0.01）. Compared with the model group， different doses of Huzhang and ribavirin significantly reduced the pathological scores of the lung tissue and lung index（P<0.01）. In addition， the mRNA levels of RSV-N， RSV-G and TNF-α in the lungs significantly decreased in the Huzhang high dose group（P<0.01）. Lipidomics analysis identified multiple significantly changed differential metabolites. Compared with the blank group， the model group showed obvious abnormal lipid metabolism， which was manifested by the elevated levels of prostaglandin（PG）， ceramide（Cer）， phosphatidylcholine（PC）， phosphatidylethanolamine（PE）， phosphatidylinositol（PI）， sphingomyelin（SM）， and the decreased levels of diglycerides（DG） and acylethanolamine（NAE）. After the intervention of low dose of Huzhang， the above lipid metabolites showed a significant reversal trend， while the intervention of high dose of Huzhang could regulate levels of PI lipids， PG lipids and PC lipids. ConclusionHuzhang can significantly reduce the viral load of lung tissue and improve lung inflammation in RSV-infected mice. The underlying mechanism may be related to the maintenance of homeostasis in pulmonary surfactant lipids such as PI and PG.
