Acta Veterinaria et Zootechnica Sinica ›› 2024, Vol. 55 ›› Issue (5): 2186-2194.doi: 10.11843/j.issn.0366-6964.2024.05.036

• BASIC VETERINARY MEDICINE • Previous Articles     Next Articles

Study on the Damage of Blood-brain Barrier by Tight Junction Protein Mediated by MMP-9 in Pseudorabies Virus-infected Mice

ZHANG Ying1, SONG Chunlian1,2, ZHANG Ying1, SHEN Hong1, SHU Xianghua1*, YANG Honggui3   

  1. 1. College of Veterinary Medicine, Yunnan Agricultural University, Kunming 650201, China;
    2. Kunming Weimude Biotechnology Co. Ltd, Kunming 650051, China;
    3. Animal Husbandry Technology Promotion Station of Luxi County, Honghe Hani and Yi Autonomous Prefecture, Luxi 652499, China
  • Received:2023-08-22 Online:2024-05-23 Published:2024-05-27

Abstract: The experiment aims to investigate the effect of pseudorabies virus (PRV) on the permeability of blood-brain barrier in mice and the correlation between matrix metalloproteinase-9 (MMP-9) and tight junction (TJ). Ninety-six Kunming SPF mice were randomly divided into control group and experimental group. Twenty-four mice of control group received nasal saline and seventy-two mice of experimental group received nasal PRV infection. The experimental groups were divided into 24 h infection group, 48 h infection group and 72 h infection group, each group consisted of 24. The clinical symptoms and the pathological lesions were observed by H&E staining. The relationship between nerve damage and viral load after PRV infection was evaluated by modified neurological score and viral load measurement in brain tissue. The permeability of blood-brain barrier was investigated by wet-dry weight method and Evans blue staining method. The correlation between MMP-9 and TJ was explored through mRNA and protein expression differences. The results showed that the degree of brain lesions increased with the extension of time, and the nerve function injury score reached the highest at the 72nd hour. There were significant differences in viral load in brain tissue 48 hours after challenge. W/D, and Evans blue concentration in brain tissue were time-dependent. The correlation between MMP-9 and TJ showed a positive correlation between MMP-9 and TJ expression. After PRV infection, the expression of MMP-9 increased, and the expression of TJ decreased. The results showed that PRV infection impairs BBB integrity and permeability through an MMP-9-mediated decrease of TJ protein expression. In summary, PRV infection may damage BBB through MMP-9-mediated destruction, which lays a foundation for further elucidation of the PRV invasion mechanism.

Key words: MMP-9, pseudorabies virus, blood-brain barrier, TJ protein

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