Abstract
OBJECTIVE:To investigate the effects of emodin on alkali burn-induced corneal inflammation and neovascularization.METHODS:The ability of emodin to target vascular endothelial growth factor receptor 2(VEGFR2)was predicted by molecular docking.The effects of emodin on the invasion,migration,and proliferation of human umbilical vein endothelial cells(HUVEC)were determined by cell counting kit-8,Transwell,and tube formation assays.Analysis of apoptosis was performed by flow cytometry.CD31 levels were examined by immunofluorescence.The abundance and phosphorylation state of VEGFR2,protein kinase B(Akt),signal transducer and activator of transcription 3(STAT3),and P38 were examined by immunoblot analysis.Corneal alkali burn was performed on 40 mice.Animals were divided randomly into two groups,and the alkali-burned eyes were then treated with drops of either 10 μM emodin or phosphate buffered saline(PBS)four times a day.Slit-lamp microscopy was used to evaluate inflammation and corneal neovascularization(CNV)in all eyes on Days 0,7,10,and 14.The mice were killed humanely 14 d after the alkali bum,and their corneas were removed and preserved at-80 ℃ until histological study or protein extraction.RESULTS:Molecular docking confirmed that emodin was able to target VEGFR2.The findings revealed that emodin decreased the invasion,migration,angiogenesis,and proliferation of HUVEC in a dose-dependent manner.In mice,emodin suppressed corneal inflammatory cell infiltration and inhibited the development of corneal neovascularization induced by alkali bum.Compared to those of the PBS-treated group,lower VEGFR2 expression and CD31 levels were found in the emodin-treated group.Emodin dramatically decreased the expression of VEGFR2,p-VEGFR2,p-Akt,p-STAT3,and p-P38 in VEGF-treated HUVEC.CONCLUSION:This study provides a new avenue for evaluating the molecular mechanisms underlying corneal inflammation and neovascularization.Emodin might be a promising new therapeutic option for corneal alkali burns.
基金项目
Fujian Major Research Grants for Young and Middleaged Health Professionals(2021ZQNZD012)
National Natural Science Foundation of China(81774369)
维普
万方数据