Acta Veterinaria et Zootechnica Sinica ›› 2024, Vol. 55 ›› Issue (11): 5299-5309.doi: 10.11843/j.issn.0366-6964.2024.11.045

• Clinical Veterinary Medicine • Previous Articles     Next Articles

Naringin Repairs Actinobacillus pleuropneumoniae-induced Lung Epithelial Barrier Damage in Mice via Multiple Pathways

Qilin HUANG1(), Chen LIU1, Xiaohan JING1, Lina HUANG2, Xiangyi PAN1, Xiongwei SHI1, Zhengying QIU1,*(), Ruihua XIN1,*()   

  1. 1. Key Laboratory of Veterinary Drug Creation, Ministry of Agriculture and Rural Affairs, and Gansu Engineering and Technology Research Centre of Chinese Veterinary Drugs, Lanzhou Institute of Animal Husbandry and Veterinary Medicine, Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
    2. State Key Laboratory of Applied Organic Chemistry, College of Pharmacy, Lanzhou University, Lanzhou 730013, China
  • Received:2023-12-26 Online:2024-11-23 Published:2024-11-30
  • Contact: Zhengying QIU, Ruihua XIN E-mail:kylin70521834@163.com;qiumoying@163.com;xinruihua@caas.cn

Abstract:

The effect of naringin (NAR) on the prevention and treatment of lung epithelial barrier damage induced by Actinobacillus pleuropneumoniae (APP) infection in mice was investigated. Forty male Kunming mice between 6 and 8 weeks of age were randomly divided into five groups, namely, the control group, the model group, the NAR low-dose group, the NAR medium-dose group and the NAR high-dose group. The drug was administered by gavage continuously for 8 d. The blank and model groups were given saline. On d 7, mice were infected with APP (1×108 CFU·mL-1, 100 μL per mouse) by tracheal intubation, and the blank group was infused with an equal volume of sterile saline, and the mice in each group were executed at 48 h after modelling, sampled and evaluated for the preventive effect of NAR. X-ray images showed that NAR reduced the APP load in the alveolar lavage fluid of mice and alleviated the pathological lung injury; moreover, NAR intervention reversed the APP-induced decrease in the expression of ZO-1, Occludin-1, and Claudin-1 tight junction proteins in the lung tissues of mice, thus promoting the repair of the lung epithelial barrier. To further explore the mechanism of NAR promoting lung epithelial barrier repair, it was found that NAR not only reduced the secretion of pro-inflammatory factors IL-6 and TNF-α, but also increased the expression of anti-inflammatory factor IL-10, and increased the expression of antioxidant enzymes SOD2 and Hmox1 in mouse lung tissues, suggesting that NAR enhances the anti-inflammatory and antioxidant capacity of the organism. In addition, NAR can inhibit the TGF-β1/Smad2/3 pathway, reduce APP-induced proliferation of lung fibrotic tissue; analysis of key proteins related to apoptosis and Tunel fluorescent labelling revealed that NAR could reduce apoptosis in a dose-dependent manner. In conclusion, NAR can repair the lung epithelial barrier damage in mice through anti-inflammatory, antioxidant, anti-fibrotic and anti-apoptotic pathways, thus effectively reversing APP-induced inflammatory lung injury and exerting the efficacy of preventing and controlling APP.

Key words: natural medicine, naringin, Actinobacillus pleuropneumoniae, pig, lung epithelial barrier injury

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