Wogonin prevents TLR4-NF-κB-medicated neuro-inflammation and improves retinal ganglion cells survival in retina after optic nerve crush.
Wogonin prevents TLR4-NF-κB-medicated neuro-inflammation and improves retinal ganglion cells survival in retina after optic nerve crush.
复制标题
汉黄芩素可预防 TLR4-NF-kappaB 介导的神经炎症，并提高视神经挤压后视网膜神经节细胞的存活率。
DOI：
10.18632/oncotarget.12700
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发表时间：
2016-11-08
期刊：
影响因子：
--
通讯作者：
Liang X
中科院分区：
文献类型：
--
作者：
Xu Y;Yang B;Hu Y;Lu L;Lu X;Wang J;Xu F;Yu S;Huang J;Liang X
慢性神经炎症参与青光眼中视网膜神经节细胞（RGC）的死亡。本研究的目的是确定汉黄芩素是否能抑制视神经挤压（ONC）后的炎症反应并挽救RGCs死亡，ONC是一种理想的青光眼动物模型。ONC模型建立后10 min腹腔注射汉黄芩素。在这项研究中，汉黄芩素治疗减少RGCs的损失和抑制RGCs的凋亡，分别表现为在ONC后第14天Brn 3a标记的RGCs增加和在第7天裂解的caspase-3表达减少。在ONC模型中，GFAP阳性胶质细胞和iba 1阳性小胶质细胞的数量增加，结合视网膜中释放的促炎细胞因子水平升高，在第7天。然而，这些反应中的大多数被抑制后汉黄芩素治疗。ONC后第1天视网膜TLR 4表达、NF-κB-P65核定位及NF-κB-P65磷酸化水平均明显升高，汉黄芩素治疗后明显降低。这些结果表明汉黄芩素通过抑制TLR 4-NF-κB通路保护ONC后RGCs的存活并抑制神经炎症反应。我们的结论是汉黄芩素可能是一种治疗青光眼的可能策略。
Chronic neuro-inflammation is involved in the death of retinal ganglion cells (RGCs) in glaucoma. The aim of this study is to determine whether wogonin can suppress inflammatory responses and rescue RGCs death after optic nerve crush (ONC), an ideal animal model of glaucoma. Wogonin was administered intraperitoneally 10 min after establishment of ONC model. In this study, wogonin treatment reduced RGCs loss and inhibited RGCs apoptosis demonstrated by the increased Brn3a labeling RGCs at day 14 and the decreased cleaved caspase-3 expression at day 7 after ONC, respectively. In ONC model, number of GFAP-positive glial cells and iba1-positive microglial cells were increased, combined of the elevated level of pro-inflammatory cytokines released in retina at day 7. However, most of these responses were inhibited after wogonin treatment. The level of TLR4 expression, NF-κB-P65 nucleus location and NF-κB-P65 phosphorylation were increased in retina at day 1 after ONC, which was significantly reduced after wogonin treatment. These results demonstrated that wogonin protected RGCs survival and suppressed neuro-inflammation in retina after ONC by inhibiting TLR4-NF-κB pathways. We conclude that wogonin could be a possible strategy for the treatment of glaucoma.