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作 者:Han Li Xi-Yu Mei Meng-Na Wang Tian-Yu Zhang Yue Zhang Bin Lu Yu-Chen Sheng
机构地区:[1]The MOE Key Laboratory for Standardization of Chinese Medicines,Shanghai Key Laboratory of Compound Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines,Institute of Chinese Materia Medica,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China [2]Center for Drug Safety Evaluation and Research,Innovation Research Institute of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China
出 处:《International Journal of Ophthalmology(English edition)》2020年第10期1538-1545,共8页国际眼科杂志(英文版)
基 金:Supported by the National Key Research and Development Program of China(No.2018YFC1707302);National Natural Science Foundation of China(No.81960748)。
摘 要: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 factorκB(NFκB)and the elevated expression of tumor necrosis factorα(TNFα),interleukin(IL)-6 and IL-1βin BV2 cells treated with D-glucose(25 mmol/L).SN attenuated iBRB dysfunction in human retinal endothelial cells(HRECs)or choroid-retinal endothelial RF/6 A cells when those cells were treated with TNFα,IL-1βor IL-6,or co-cultured with microglia cells stimulated by D-glucose.Moreover,SN restored the decreased protein expression of tight junctions(TJs)in TNFα-treated HRECs and RF/6 A cells.CONCLUSION:SN not only alleviate iBRB dysfunction via directly inhibiting retinal endothelial injury caused by TNFα,IL-1βor IL-6,but also reduce the release of TNFα,IL-1βand IL-6 from microglia cells by abrogating hyperglycemia-mediated the activation of microglia cells.
关 键 词:SCUTELLAREIN blood-retinal-barrier tight junctions inflammation tumor necrosis factorα
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