内皮抑素对小鼠脉络膜新生血管抑制作用的表达基因的GO分析

A GO analysis of gene expression on the inhibitory effect of endostatin on mouse choroidal neovascularization

目的探讨内皮抑素对C57BL/6J小鼠脉络膜新生血管的抑制作用的基因表达及其作用机制。方法应用532nm固体激光机,制造C57BL/6J小鼠脉络膜新生血管模型,分为空白组、对照组和实验组。其中空白组不做任何处理,对照组玻璃体腔内注射生理盐水2μL;实验组玻璃体腔内注射内皮抑素(恩度)2μL(0.01mg)。将造模成功的对照组和有明显抑制的实验组小鼠组织选取了4个样本进行杂交,进行基因芯片检测。对实验结果进行3万多个基因位点的基因芯片分析,比较实验组和对照组基因表达的差异,选取其中表达差异大于1.5倍且P≤0.05的基因。结果用CD105进行免疫组化染色可见实验组新生血管表达明显低于对照组。应用基因芯片结果显示:实验组与对照组相比上调的基因有116个,下调的基因有106个。通过GO分析,发现内皮抑素显示出了抑制细胞活性、抑制细胞生长的特性但并不启动免疫系统活性甚至可抑制免疫系统活性的特性。结论内皮抑素可能通过抑制内皮细胞的活性以及移行并协同抑制免疫系统,进而抑制新生血管的生成。

Objective To study the gene expression on the inhibitory effect of endostatin on choroidal neovascularization in C57BL/6J mice and the mechanisms. Methods Photocoagulation using 532 nm diode laser was performed to establish a CNV model in mice＇s eye. The mice were randomly divided into three groups： blank group （model group） ; endostatin group （experimental group）, in which endostatin of 0.01 mg/2 μL was given intravitreally; and saline group （control group）, which received intravitreal injection of 2 μL of 0.9 g/L saline. Four samples selected respectively from experimental group and control group were used to complete the gene expression profiling analysis. By comparing the differences of gene expression between the two groups, we selected the genes with expression difference ≥ 1. 5 times and P ≤ 0. 05. Results CD105 marking showed that choroidal neovascularization was significantly lower in endostatin group than in control group. The gene expression analysis showed that 116 genes were up-regulated and 106 genes were down-regulated in endostatin group compared with control group. GO analysis indicated that endostatin could inhibit cell activity and growth, but did not initiate the activity of the immune system, and even suppress it. Gonclusion Endostatin can inhibit the activity and locomotion of endothelial cells and synergically inhibits the immune system, thus suppressing choroidal neovascular- ization.