Suppression of experimental choroidal neovascularization by curcumin in mice.
Suppression of experimental choroidal neovascularization by curcumin in mice.
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DOI：
10.1371/journal.pone.0053329
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Xie P;Zhang W;Yuan S;Chen Z;Yang Q;Yuan D;Wang F;Liu Q
探讨姜黄素对实验性脉络膜新生血管（CNV）形成的影响及其细胞和分子机制。在激光诱导CNV之前，每天用腹膜内注射姜黄素预处理C57 BL/6 N小鼠3天，并持续药物治疗直至研究结束。在激光光凝后第7天和第14天，通过视网膜色素上皮（RPE）-脉络膜平坦载玻片的荧光素标记葡聚糖血管造影术分析CNV面积，并在第14天通过荧光素血管造影术（FA）评估CNV渗漏。在第3天通过免疫组织化学在RPE-脉络膜平板上评价F4/80阳性巨噬细胞和GR-1阳性粒细胞的浸润。在第3天通过实时PCR（F4/80）和蛋白质印迹（GR-1）定量它们在RPE-脉络膜复合体中的表达。在第3天通过ELISA检测RPE脉络膜血管内皮生长因子（VEGF）、肿瘤坏死因子（TNF）-α、单核细胞趋化蛋白（MCP）-1和细胞间粘附分子（ICAM）-1的水平。在第3天对CNV病变的冷冻切片进行F4/80和VEGF的双重免疫染色。通过蛋白质印迹法测定RPE-脉络膜中核因子（NF）-κB和缺氧诱导因子（HIF）-1α的表达。姜黄素处理的小鼠具有比载体处理的小鼠显著更少的CNV面积（P<0.05）和CNV渗漏（P<0.001）。姜黄素能显著抑制F4/80阳性巨噬细胞（P<0.05）和GR-1阳性粒细胞浸润（P<0.05）。VEGF主要表达于激光损伤部位F4/80阳性的巨噬细胞，姜黄素处理后VEGF表达明显降低（P<0.01）。姜黄素可抑制RPE脉络膜中TNF-α（P<0.05）、MCP-1（P<0.05）和ICAM-1（P<0.05）的表达，抑制核提取物中NF-κB的活化（P<0.05）和HIF-1α的活化（P<0.05）。姜黄素治疗可抑制CNV的发展以及炎症和血管生成过程，包括NF-κB和HIF−1α激活、炎症和血管生成细胞因子的上调以及浸润性巨噬细胞和粒细胞。这提供了姜黄素补充剂作为抑制年龄相关性黄斑变性（AMD）相关CNV的治疗策略的有效性的分子和细胞证据。
To investigate the effects of curcumin on the development of experimental choroidal neovascularization (CNV) with underlying cellular and molecular mechanisms. C57BL/6N mice were pretreated with intraperitoneal injections of curcumin daily for 3 days prior to laser-induced CNV, and the drug treatments were continued until the end of the study. The CNV area was analyzed by fluorescein-labeled dextran angiography of retinal pigment epithelium (RPE)-choroid flat mounts on day 7 and 14, and CNV leakage was evaluated by fluorescein angiography (FA) on day 14 after laser photocoagulation. The infiltration of F4/80 positive macrophages and GR-1 positive granulocytes were evaluated by immunohistochemistry on RPE-choroid flat mounts on day 3. Their expression in RPE-choroid complex was quantified by real-time PCR (F4/80) and Western blotting (GR-1) on day 3. RPE-choroid levels of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 were examined by ELISA on day 3. Double immunostaining of F4/80 and VEGF was performed on cryo-sections of CNV lesions on day 3. The expression of nuclear factor (NF)-κB and hypoxia-inducible factor (HIF)−1α in the RPE-choroid was determined by Western blotting. Curcumin-treated mice had significantly less CNV area (P<0.05) and CNV leakage (P<0.001) than vehicle-treated mice. Curcumin treatment led to significant inhibition of F4/80 positive macrophages (P<0.05) and GR-1 positive granulocytes infiltration (P<0.05). VEGF mainly expressed in F4/80 positive macrophages in laser injury sites, which was suppressed by curcumin treatment (P<0.01). Curcumin inhibited the RPE-choroid levels of TNF-α (P<0.05), MCP-1 (P<0.05) and ICAM-1 (P<0.05), and suppressed the activation of NF-κB in nuclear extracts (P<0.05) and the activation of HIF−1α (P<0.05). Curcumin treatment led to the suppression of CNV development together with inflammatory and angiogenic processes including NF-κB and HIF−1α activation, the up-regulation of inflammatory and angiogenic cytokines, and infiltrating macrophages and granulocytes. This provides molecular and cellular evidence of the validity of curcumin supplementation as a therapeutic strategy for the suppression of age-related macular degeneration (AMD)-associated CNV.
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影响因子：
3.7
作者：
Chen H;Liu B;Lukas TJ;Neufeld AH
通讯作者：
Neufeld AH
DOI：
10.1152/ajpgi.00138.2002
发表时间：
2003-01-01
影响因子：
4.5
作者：
Gukovsky, I;Reyes, CN;Pandol, SJ
通讯作者：
Pandol, SJ
影响因子：
12.6
作者：
Hanai, Hiroyuki;Iida, Takayuki;Koide, Yukio
通讯作者：
Koide, Yukio
影响因子：
3.1
作者：
Chen, Dong;Nie, Min;Bian, Zhuan
通讯作者：
Bian, Zhuan
影响因子：
2
作者：
Hara, Ryuhei;Inomata, Yasuya;Tanihara, Hidenobu
通讯作者：
Tanihara, Hidenobu