利用腺相关病毒AAV1探究顺铂诱导的血管纹损伤中Gasdermin D的作用机制

doi:10.6040/j.issn.1673-3770.0.2025.041

Abstract

Abstract: Objective To investigate the morphological effects of AAV1-GSDMD-GFP virus, containing the gene fragment of the key pyroptosis execution protein Gasdermin D(GSDMD)labeled with green fluorescent protein(GFP), on the stria vascularis(SV)of Gsdmd knockout(Gsdmd ^-/-)mice after cisplatin treatment. Methods Gsdmd ^-/- mice were divided into four groups: Control(Gsdmd ^-/-), blank virus control(Gsdmd ^-/-+AAV1-GFP), cisplatin-treated(Gsdmd ^-/-+Cisplatin), and GSDMD-rescued(Gsdmd ^-/-+AAV1-GSDMD-GFP+Cisplatin). Morphological changes in the SV were analyzed via fluorescence staining(Phalloidin, Kcnq1, and GS-IB₄). Results The Gsdmd ^-/-+Cisplatin group exhibited resistance to cisplatin-induced ototoxicity. However, successful reintroduction of GSDMD via AAV1-GSDMD-GFP resulted in significant morphological abnormalities in the SV, including vascular dendritic fragmentation and cellular structural disruption, indicating that GSDMD restoration reversed the resistance phenotype. Conclusion Resistance to cisplatin ototoxicity in the stria vascularis of Gsdmd ^-/- mice can be reversed by AAV1 backfilling of GSDMD.

Key words: Adeno-associated virus, Pyroptosis, Cisplatin ototoxicity, Stria Vascularis Injury

CLC Number:

R764

ZHANG Xiaohan, ZHU Liya, XIAO Yu, FU Xiaolong. Investigating the mechanism of Gasdermin D in cisplatin-induced stria vascularis injury using adeno-associated virus AAV1[J].Journal of Otolaryngology and Ophthalmology of Shandong University, 2026, 40(2): 29-34.

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Investigating the mechanism of Gasdermin D in cisplatin-induced stria vascularis injury using adeno-associated virus AAV1

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