Liu Yang, Sha Tong-Tong, Sun Guang-Li, Liang Shen-Zhi, Yu Fang-Fang
Department of Ophthalmology, First Affiliated Hospital of Zhengzhou University, No.1 jianshe dong road, Zhengzhou, 450052, Henan, China.
Department of Environmental Health, School of Public Health, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, 450001, Henan, China.
Sci Rep. 2025 Jul 1;15(1):22227. doi: 10.1038/s41598-025-07745-5.
The proteomics were used to investigate the mechanism of sodium selenite causing age-related nuclear cataract in rats. Four pregnant Sprague-Dawley rats were selected, and the neonatal rats were randomly divided into three groups after natural delivery. The rats received subcutaneous injection of sodium selenite in LSe (10 µmol/kg·b.w) and HSe (20 µmol/kg·b.w) group, the rats received equal volume of normal saline in the control group. On postnatal day 21, these rats were sacrificed. Total proteins were extracted from lens tissues for proteomic analysis. Hematoxylin-eosin staining was used to determine the lens lesions. Immunohistochemistry staining and Western blot were used to verify the key proteins. In this study, the cataracts were observed in LSe and HSe group. In the control group, lens epithelial cells (LECs) were lined up with the same morphology, the lens fibers were arranged tightly and neatly. The base of LECs was closely connected with the lens fibers. In LSe and HSe group, the morphology of LECs were irregular, the lens fibers were disordered, vesicles and water cracks were observed within the fiberboard. Proteomic analysis identified 104 differentially expressed proteins (57 up-regulated and 47 down-regulated proteins), which were of great significance for the development of age-related nuclear cataract. KEGG pathway enrichment analysis revealed that protein processing in endoplasmic reticulum pathway was significantly enriched in the HSe group. According to the betweenness centrality, PPI network shown that Hspa5 was the hub protein, which was crucial for understanding and treating age-related nuclear cataract. Immunohistochemistry staining results showed the Hspa5, Manf and Calr were significantly up-regulated in LSe and HSe group. Western blot results showed the Hspa5 and Calr were significantly up-regulated in LSe and HSe group, which were consistent with our proteomic results. In conclusion, moderate sodium selenite induced endoplasmic reticulum stress, and led to age-related nuclear cataract of rats, in which Hspa5 played a key role.
蛋白质组学被用于研究亚硒酸钠导致大鼠年龄相关性核性白内障的机制。选取4只怀孕的Sprague-Dawley大鼠，自然分娩后将新生大鼠随机分为三组。LSe（10 µmol/kg·体重）和HSe（20 µmol/kg·体重）组大鼠皮下注射亚硒酸钠，对照组大鼠注射等量生理盐水。出生后第21天，处死这些大鼠。从晶状体组织中提取总蛋白进行蛋白质组学分析。采用苏木精-伊红染色确定晶状体病变情况。免疫组织化学染色和蛋白质印迹法用于验证关键蛋白。本研究中，LSe组和HSe组观察到白内障形成。对照组中，晶状体上皮细胞（LECs）形态排列一致，晶状体纤维排列紧密整齐。LECs基部与晶状体纤维紧密相连。在LSe组和HSe组中，LECs形态不规则，晶状体纤维排列紊乱，在纤维板内观察到囊泡和水裂。蛋白质组学分析鉴定出104种差异表达蛋白（57种上调蛋白和47种下调蛋白），这对年龄相关性核性白内障的发生发展具有重要意义。KEGG通路富集分析显示，内质网蛋白加工通路在HSe组中显著富集。根据介数中心性，蛋白质-蛋白质相互作用（PPI）网络显示Hspa5是枢纽蛋白，这对于理解和治疗年龄相关性核性白内障至关重要。免疫组织化学染色结果显示，Hspa5、Manf和Calr在LSe组和HSe组中显著上调。蛋白质印迹结果显示，Hspa5和Calr在LSe组和HSe组中显著上调，这与我们的蛋白质组学结果一致。总之，适量亚硒酸钠诱导内质网应激，导致大鼠年龄相关性核性白内障，其中Hspa5起关键作用。
