Effect of Dingchuan Granule (定喘颗粒) on Lung Tissue Oxidative Stress and Nrf2/Keap1/HO-1/NQO1 Pathway in Respiratory Syncytial Virus Pneumonia Model Rats
10.13288/j.11-2166/r.2025.15.013
- VernacularTitle:定喘颗粒对呼吸道合胞病毒肺炎模型大鼠肺组织氧化应激及Nrf2/Keap1/HO-1/NQO1信号通路的影响
- Author:
Lai ZHANG
1
;
Xiuying ZHANG
2
;
Chenhao WEI
1
;
Shiyao ZHANG
1
;
Zhaoyang LI
1
;
Rui WANG
1
;
Hangyu ZHAO
1
Author Information
1. The First Clinical College of Liaoning University of Traditional Chinese Medicine,Shenyang,116600
2. The First Affiliated Hospital of Liaoning University of Traditional Chinese Medicine
- Publication Type:Journal Article
- Keywords:
respiratory syncytial virus;
pneumonia;
oxidative stress;
nuclear factor (erythroid derived 2)-like 2;
Dingchuan Granule (定喘颗粒)
- From:
Journal of Traditional Chinese Medicine
2025;66(15):1588-1596
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the potential mechanism of Dingchuan Granule (定喘颗粒, DG) in the treatment of respiratory syncytial virus (RSV) pneumonia. MethodsA total of 60 male Sprague Dawley (SD) rats were randomly divided into control group, model group, ribavirin group, DG low-dose group, DG middle-dose group, and DG high-dose group, with 10 rats in each group. Except for the control group, rats were administrated with RSV via intranasal drip. After model establishment, the DG low-, middle-, and high-dose groups were administrated via oral gavage with DG at 3.47, 6.93, and 13.86 g/(kg·d) respectively, while the ribavirin group was administrated via oral gavage with ribavirin at 15.75 mg/(kg·d). The drug was given once daily for one week. The rats in the control group and the model group were not given any drug, only subjected to the grasping action. Twenty-four hours after the last administration, the pathological changes of lung tissues were observed and scored using HE staining. The levels of serum inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), were detected by colorimetry. The protein levels of nuclear factor (erythroid derived 2)-like 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase 1 (HO-1), and NAD(P)H quinone dehydrogenase 1 (NQO1) in lung tissues were measured by Western Blot. The RSV load as well as the gene expression levels of Nrf2, Keap1, HO-1, and NQO1 in lung tissues were determined by qRT-PCR. The level of reactive oxygen species (ROS) in rat lung tissues was detected using chemiluminescence. The levels of glutathione (GSH) and malondialdehyde (MDA) in rat lung tissues were measured by a microassay. ResultsCompared with the control group, other groups had significant increases in pathological score of lung tissue, RSV load, levels of ROS, MDA, serum TNF-α, IL-1β, and IL-6; decrease in GSH level, increases in expression level of Keap1 protein and its mRNA in lung tissue, and significant decrease in levels of Nrf2, HO-1, expression level of NQO1 protein and its mRNA (P<0.05). Compared with the model group, all the above-mentioned indicators in the DG low-, middle-, and high-dose groups and the ribavirin group were improved to varying degree (P<0.05). The levels of serum TNF-α, IL-1β, and IL-6 in rats of DG dose groups showed a dose-dependent pattern, the DG high-dose group exhibiting the best effect (P<0.05). The DG high-dose group was superior to the DG low- and middle-dose groups in reducing the levels of ROS and MDA, and increasing the level of GSH in lung tissues (P<0.05). The DG high-dose group and the ribavirin group had better effect than the DG middle-dose group in reducing the RSV load (P<0.05). The DG high-dose group was superior to the ribavirin group in improving the protein levels of Nrf2, Keap1, HO-1, and NQO1 (P<0.05). ConclusionDG could inhibit oxidative stress by regulating the Nrf2/Keap1/HO-1/NQO1 signaling pathway to improve pulmonary inflammation and treat RSV pneumonia, with the DG high-dose group showing the best effect.