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閲覧数:773
ID 20160325_K492
アイテムタイプ Article
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本文 K492 Shimouchi Akito_TD.pdf
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Last updated : Apr 25, 2016
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タイトル 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
著者
下内, 昭人 (Shimouchi, Akito)
上位タイトル
Japanese Journal of Ophthalmology Vol.60, No.1  (2016. 1) ,p.51- 61
識別番号
ISSN
0021-5155
DOI 10.1007/s10384-015-0415-z
その他
PMID:26407617
博士論文情報
学位授与番号 10107A492
学位授与年月日 2016-03-25
学位名 博士(医学)
学位授与機関 旭川医科大学
抄録 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.
キーワード
Hesperetin
Ischemia–reperfusion
Neuroprotection
Retina
Inflammation
注記 First online: 25 September 2015

The final publication is available at Springer via http://dx.doi.org/10.1007/s10384-015-0415-z
言語
eng
資源タイプ application/pdf
ジャンル Thesis or Dissertation
著者版フラグ ETD
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