[1]杨秀梅,王雨生. MEK/ERK参与大鼠脉络膜新生血管基质金属蛋白酶-2和基质金属蛋白酶-9的表达调控[J].眼科新进展,2015,35(6):501-506.[doi:10.13389/j.cnki.rao.2015.0137]
　YANG Xiu-Mei,WANG Yu-Sheng. Contribution of MEK/ERK pathway in regulation of MMP-2 and MMP-9 expression in rat choroidal neovascularization[J].Recent Advances in Ophthalmology,2015,35(6):501-506.[doi:10.13389/j.cnki.rao.2015.0137]
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 MEK/ERK参与大鼠脉络膜新生血管基质金属蛋白酶-2和基质金属蛋白酶-9的表达调控
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《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
35卷
期数:
2015年6期
页码:
501-506
栏目:
实验研究
出版日期:
2015-06-05

文章信息/Info

Title:
 Contribution of MEK/ERK pathway in regulation of MMP-2 and MMP-9 expression in rat choroidal neovascularization
作者:
 杨秀梅; 王雨生
 100700　北京市，北京军区总医院眼科
Author(s):
 YANG Xiu-Mei; WANG Yu-Sheng
 Department of Ophthalmology ,Beijing General Command Hospital, Beijing 100700 , China
关键词:
 ; 基质金属蛋白酶-2; 基质金属蛋白酶-9; 脉络膜新生血管; 大鼠
Keywords:
 ; matrix metalloproteinase-2 ;  matrix metalloproteinase-9 ;  choroidal neovascularization ;  rat
DOI:
10.13389/j.cnki.rao.2015.0137
文献标志码:
A
摘要:
 目的　探讨基质金属蛋白酶２（ｍａｔｒｉｘｍｅｔａｌｌｏｐｒｏｔｅｉｎａｓｅ-２，ＭＭＰ-２）和ＭＭＰ-９在大鼠脉络膜新生血管（ｃｈｏｒｏｉｄａｌｎｅｏｖａｓｃｕｌａｒｉｚａｔｉｏｎ，ＣＮＶ）内的表达及其可能的调控机制。方法　将２３只成年雄性棕色挪威大鼠随机分为２组，一组为玻璃体内注药组，视网膜光凝后即刻玻璃体内注射３μＬＰＤ９８０５９；另一组为单纯光凝组，单纯行视网膜光凝。观察时间为光凝后３ｄ、７ｄ和１４ｄ。各时间点处死大鼠后摘除眼球，免疫组织化学法和免疫荧光法观察ＭＭＰ-２和ＭＭＰ-９在大鼠ＣＮＶ内不同时间点的表达特点。眼底荧光血管造影（ｆｕｎｄｕｓｆｌｕｏｒｅｓｃｅｎｃｅａｎｇｉｏｇｒａｐｈｙ，ＦＦＡ）和ＨＥ法观察玻璃体内注射ＰＤ９８０５９对ＣＮＶ生成的作用， Ｗｅｓｔｅｒｎｂｌｏｔｔｉｎｇ检测观察注药对ＣＮＶ内ＭＭＰ-２和ＭＭＰ-９表达的影响。结果　光凝后３ｄ，单纯光凝组光凝区即有ＭＭＰ-２和ＭＭＰ-９的阳性表达；光凝后７ｄ和１４ｄ二者表达均逐渐增强。光凝后７ｄ，玻璃体内注药组ＭＭＰ-２和ＭＭＰ-９均显著被抑制，分别被抑制约６９％和８０％。Ｗｅｓｔｅｒｎｂｌｏｔｔｉｎｇ检测结果示玻璃体内注射组可显著抑制ＥＲＫ的磷酸化，光凝后３ｄ及７ｄ的抑制率分别为５４％和６０％，而对ＥＲＫ总量的表达无明显作用。ＦＦＡ和ＨＥ显示，玻璃体内注药组光凝后１４ｄ减少光凝局部ＣＮＶ的荧光素渗漏约５１％，抑制ＣＮＶ厚度达５７％。免疫荧光法检测结果示光凝后７ｄ，玻璃体内注药组抑制ＭＭＰ-２和ＭＭＰ-９的表达分别为７３％和６４％。结论　ＭＭＰ-２和ＭＭＰ-９参与了大鼠ＣＮＶ的生成，光凝后３ｄ即有阳性表达，至光凝后１４ｄ表达进一步增强，ＭＥＫ／ＥＲＫ通路至少部分参与了ＭＭＰ-２和ＭＭＰ-９在ＣＮＶ内的生成调控。
Abstract:
 Objective To investigate the expression and regulation mechanism of matrix metalloproteinase-2 ( MMP-2 ) and MMP-9 in rat choroidal neovascularizaiton (CNV). Methods Twenty-three adult male Brown Norway ( BN) rats were divided int0 2 groups :the PD98059 treated group and the simple photocoagulation group. Both eyes of each animal were induced by laser photocoagulation with 532 nm laser , the animals in PD98059 treated group were intravitreous injected the PD98059 timely immediately after photocoagulation. At 3 days , 7 days and 14 days after photocoagulation , the expression of MMP-2 and MMP-9 were examined by HE ,immunohistochemistry staining and immunofluorescence staining, the effect of intravitreous injection of PD98059 0n CNV formation was observed by FFA and HE staining , and the effect of intravitreous injection of PD98059 0n MMP-2 and MMP-9 expression were detected by Western blotting. Results At 3 days after photocoagulation ,the expression of MMP-2 and MMP-9 in the simple photocoagulation group were positive , and increased at 7 days and 14 days after photocoagulation. At 7 days after photocoagulation, the expression of MMP-2 and MMP-9 were obviously inhibited by PD98059,the inhibitive rate were 6g% and 80% .respectively. Intravitreous injection of PD98059 dramatically decreased the level of p-ERK to 54% and 60% at 3 days and 7 days after photocoagulation, respectively, while had no effect on ERK expression. PD98059 was able to inhibit the growth of CNV t0 57% by HE staining and decrease the leakage t0 51% by FFA at 14 days after photocoagulation. Immunofluorescence staining had the similar result as immunohistochemistry which showed PD98059 attenuated the expression of MMP-2 and MMP-9 t0 73% and 64% ,respectively. Conclrision MMP-2 and MMP-9 are involved in the development of CNV ,positively express at 3 days and increase at 14 days after photocoagulation. MEK/ERK pathway at least partly regulate the expression of MMP-2 and -9 during the development of CNV.

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备注/Memo

备注/Memo:
 国家自然科学基金（编号：８１０７０７４８）；国家重点基础研究发展计划（９７３）项目（编号：２０１１ＣＢ５１０２００）
更新日期/Last Update: 2015-06-01