期刊
INTERNATIONAL JOURNAL OF OPHTHALMOLOGY
卷 13, 期 10, 页码 1538-1545出版社
IJO PRESS
DOI: 10.18240/ijo.2020.10.05
关键词
scutellarein; blood-retinal-barrier; tight junctions; inflammation; tumor necrosis factor alpha
资金
- National Key Research and Development Program of China [2018YFC1707302]
- National Natural Science Foundation of China [81960748]
AIM: To investigate the alleviation of scutellarein (SN) against inner blood-retinal-barrier (iBRB) dysfunction in microglia cells stimulated by hyperglycemia and to elucidate the engaged mechanism. METHODS: Microglia BV2 cells were stimulated by using 25 mmol/L D-glucose. The same concentration of mannitol (25 mmol/L) was applied as an isotonic contrast. Real-time PCR, Western-blot assay and immunofluorescence staining assay was performed. The dysfunction of iBRB in vitro was detected by using transendothelial electrical resistance (TEER) assay. Additionally, the leakage of fluorescein isothiocyanate (FITC)-conjugated dextran (70 kDa) was detected. RESULTS: SN abrogated microglia BV2 cells activation and reduced the phosphorylated activation of extracellular signal-regulated protein kinase (ERK) 1/2. SN also decreased the transcriptional activation of nuclear factor kappa B (NF kappa B) and the elevated expression of tumor necrosis factor alpha (TNF alpha), interleukin (IL)-6 and IL-1 beta in BV2 cells treated with D-glucose (25 mmol/L). SN attenuated iBRB dysfunction in human retinal endothelial cells (HRECs) or choroid-retinal endothelial RF/6A cells when those cells were treated with TNF alpha, IL-1 beta or IL-6, or co-cultured with microglia cells stimulated by D-glucose. Moreover, SN restored the decreased protein expression of tight junctions (TJs) in TNF alpha-treated HRECs and RF/6A cells. CONCLUSION: SN not only alleviate iBRB dysfunction via directly inhibiting retinal endothelial injury caused by TNF alpha, IL-1 beta or IL-6, but also reduce the release of TNF alpha, IL-1 beta and IL-6 from microglia cells by abrogating hyperglycemia-mediated the activation of microglia cells.
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