昆明医科大学学报2026，Vol.47Issue(3)：45-53,9.DOI:10.12259/j.issn.2095-610X.S20260305
雷公藤红素干预Transcription Factor EB介导的溶酶体生物发生障碍抑制白内障形成的分子机制
Molecular Mechanism of Celastrol Intervening in TFEB-Mediated Lysosomal Biogenesis Dysfunction Inhibiting Cataract Formation
摘要
Abstract
Objective This study aims to investigate whether celastrol(Cel)inhibits cataract formation by activating the transcription factor EB(TFEB)-mediated lysosomal biosynthesis pathway.Methods An oxidative stress model in human lens epithelial cells induced by H2O2 and a rat cataract model induced by selenite were employed.Cells were divided into control,model,Cel intervention,Cel+TFEB siRNA,or Cel+MHY1485 groups(n=5).45 neonatal mice were divided into control,model,low-,medium-,and high-dose Cel groups(n=9).Cell viability was assessed by the CCK-8 assay,TFEB nuclear translocation was observed by immunofluorescence staining.Protein expression of LAMP1 and CTSB was detected by Western blot,lysosome quantity was assessed by LysoTracker Red staining.Lens opacity was observed and graded using the Bahmani standard under slit lamp microscopy,and lens morphology was observed by hematoxylin and eosin staining.TFEB siRNA and an mTOR activator(MHY1485)were also used to validate the mechanism of action of Cel.Results Compared with the model group,the Cel intervention group significantly increased TFEB nuclear translocation efficiency by approximately 2.1-fold(P＜0.000 1)and significantly upregulated the expression of lysosomal function-related proteins(all P＜0.001).LysoTracker Red staining showed that Cel intervention group reversed the H2O2-induced decrease in lysosome quantity(P＜0.000 1).In the animal model,Cel intervention group significantly reduced lens opacity(P＜0.05).These positive effects of Cel were significantly antagonized by TFEB siRNA or the mTOR activator MHY1485(P＜0.001).Conclusion Cel promotes TFEB nuclear translocation by inhibiting the mTOR signaling pathway,enhances lysosomal biogenesis,improves lens protein homeostasis,and thereby suppresses cataract formation.This study provides a theoretical basis for non-surgical cataract treatment targeting TFEB.关键词
雷公藤红素/转录因子EB/溶酶体/白内障/mTORKey words
Celastrol/Transcription factor EB/Lysosome/Cataract/mTOR分类
医药卫生引用本文复制引用
祁春梅,李秀慧,张智慧..雷公藤红素干预Transcription Factor EB介导的溶酶体生物发生障碍抑制白内障形成的分子机制[J].昆明医科大学学报,2026,47(3):45-53,9.基金项目
河北省卫生健康委员会科研项目(20230214) （20230214）
