網膜虚血再灌流障害における分散ヘスペレチンの神経保護効果

• Material Type: 博士論文
• ISSN: 0021-5155
• Title: 網膜虚血再灌流障害における分散ヘスペレチンの神経保護効果
• Volume: 60 1
• Author/Editor: 下内, 昭人
• Publication Date: 2016-01
• Publication Date (W3CDTF): 2016-01
• Alternative Title: Neuroprotective effect of water-dispersible hesperetin in retinal ischemia reperfusion injury
• Periodical title: Japanese Journal of Ophthalmology
• Degree grantor/type: 旭川医科大学
• Date Granted: 2016-03-25
• Date Granted (W3CDTF): 2016-03-25
• Dissertation Number: 甲第492号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第492号
• Text Language Code: eng
• Subject Heading: Hesperetin; Ischemia–reperfusion; Neuroprotection; Retina; Inflammation
• Note (General): First online: 25 September 2015 The final publication is available at Springer via http://dx.doi.org/10.1007/s10384-015-0415-z; Purpose To determine whether water-dispersible hesperetin (WD-Hpt) can prevent degeneration of ganglion cell neurons in the ischemic retina. Methods Ischemia reperfusion (I/R) injury was induced by increasing the intraocular pressure of mice to 110 mmHg for 40 min. Mice received daily intraperitoneal injections with either normal saline (NS, 0.3 ml/day) or WD-Hpt (0.3 ml, 200 mg/kg/day). Reactive oxygen species (ROS) was assessed by dihydroethidium and nitrotyrosine formation. Inflammation was estimated by microglial morphology in the retina. Lipopolysaccharide (LPS)-stimulated BV-2 cells were used to explore the anti-inflammatory effect of WD-Hpt on activated microglia by quantifying the expression of IL-1β using real-time quantitative reverse transcription-polymerase chain reaction. Ganglion cell loss was assessed by immunohistochemistry of NeuN. Glial activation was quantified with glial fibrillary acidic protein (GFAP) immunoreactivity. Apoptosis was evaluated with a terminal deoxynucleotidyl transferase (TUNEL) assay and immunohistochemistry of cleaved caspase-3. Phosphorylation of extracellular signal-regulated kinase (p-ERK) was surveyed by western blotting. Results WD-Hpt decreased I/R-induced ROS formation. WD-Hpt alleviated microglial activation induced by I/R and reduced mRNA levels of IL-1β in LPS-stimulated BV-2. I/R resulted in a 37 % reduction in the number of ganglion cells in the NS-treated mice, whereas the reduction was only 5 % in the WD-Hpt-treated mice. In addition, WD-Hpt mitigated the immunoreactivity of GFAP, increased expression of cleaved caspase-3, increased number of TUNEL positive cells and p-ERK after I/R. Conclusions WD-Hpt protected ganglion cells from I/R injury by inhibiting oxidative stress and modulating cell death signaling. Moreover, WD-Hpt had an anti-inflammatory effect through the suppression of activated microglia.; identifier:PMID:26407617; 開始ページ : 51; 終了ページ : 61
• DOI: info:doi/10.1007/s10384-015-0415-z; https://doi.org/info:doi/10.1007/s10384-015-0415-z
• Persistent ID (NDL): info:ndljp/pid/10211583; https://dl.ndl.go.jp/pid/10211583
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2016-11-02T12:02:18+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
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• Periodical Title (URI): http://amcor.asahikawa-med.ac.jp/modules/xoonips/detail.php?id=20160325_K492
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp