FK228抑制鼠视网膜新生血管的机制研究

The mechanism research of inhibitory effects of FK228 on retinal neovascularization

目的:探讨组蛋白去乙酰化酶抑制剂(Histone deacetylase inhibitor,HDACI)FK228抑制视网膜新生血管形成的机制。方法:将鼠龄为7d的C57BL/6J幼鼠置于75%浓度的氧环境中连续生活5d,建立髙氧诱导的血管增生性视网膜病变幼鼠模型。随机分为正常对照组、给氧对照组及治疗组(幼鼠玻璃体腔内注射FK228250ng,对侧眼注射相同体积的二甲基亚砜溶液作为对照)。并采用免疫组织化学法检测缺氧诱导因子α亚基(Hypoxia-inducible factor-1α,HIF-1α)和血管内皮细胞生长因子(Vascular endothelial growth factor,VEGF),观察FK228抑制视网膜新生血管的机制。结果:(1)空白组和治疗组的HIF-1α免疫细胞阳性率没有明显差异(P>0.05)。对照组与空白组和治疗组这两组的HIF-1α免疫细胞阳性率均有明显差异(P<0.05)。(2)空白组和治疗组的VEGF免疫细胞阳性率没有明显差异(P>0.05)。对照组与空白组和治疗组这两组的VEGF免疫细胞阳性率均有明显差异(P<0.05)。结论:FK228抑制视网膜新生血管形成的机制可能与其抑制HIF-1α活性从而下调VEGF的表达有关。

Objective：To explore the mechanism of the inhibitory effects of FK228 on retinal nevoascularization. Methods： One-week-old C57BL/6J mice were put into the environment with 75% oxygen for 5 days to establish models of vascular proliferation retinopathy. These mice were divided into normal control,high oxygen control and treatment groups（One eye of each mouse received an intravitreal injection of 250ng of FK228,and the same volume of DMSO（dimethylsuffoxide） was injected into the other eye of the mice both in these two groups as a control）. Hypoxia-inducible factor-1α （HIF-1α） and vascular endothelial growth factor（ VEGF ）expression were examined by immunohistochemistry. The inhibitory effects of FK228 on retinal nevoascularization were evaluated. Results：（1 ）There was no significant difference in HIF-1 ctpositive rate between normal group and treatment group（P〉0.05）;HIF-1α positive rate of control groups was higher than that in normal group and treatment group with significant difference among them（P〈0.05 ）.（ 2）There was no significant difference in VEGF positive rate between normal group and treatment group（P〉0.05）;VEGF positive rate in control groups was higher than that in normal group and treatment group with significant difference among them（P〈0.05 ）. Conclusions：The mechanism of inhibitory effects of FK228 on retinal neovascularization is associated with the fact that FK228 inhibits activities of HIF-1α and deduce number of VEGF.