甲酰肽受体Fpr2在氧诱导视网膜病变小鼠新生血管形成中的作用及相关机制研究

目的 探讨甲酰肽受体Fpr2在氧诱导视网膜病变(OIR)小鼠中对胶质细胞改变的影响,并探讨其在新生血管形成中的作用及机制.方法 将新生C57BL/6J小鼠、Fpr2-/-小鼠分别诱导建立OIR模型后分为氧诱导组和Fpr2-/-氧诱导组.正常对照组和Fpr2-/-组小鼠正常环境饲养.收集各组小鼠视网膜组织并制作成冰冻切片...

Role of formyl peptide receptor Fpr2 on neovascularization in rats with oxygen-induced retinopathy and its mechanism

Objective　To investigate the effect of the formyl peptide receptor (Fpr2) on the changes of glial cells in oxygen-induced retinopathy (OIR), and to explore its role and mechanism in neovascularization.Methods　OIR model was induced in newborn C57BL / 6J mice and Fpr2^-/- mice and they were divided into oxygen induced group and Fpr2^-/- oxygen induced group of OIR model. The mice in normal control group and Fpr2^-/- group were fed in normal environment. The retinal tissues of mice in each group were collected and made into frozen sections and stained with immunofluorescence staining. Then, the changes of glial cell markers including Vimentin, glial fibrillary acidic protein (GFAP) and ionized calcium binding aptamer 1 (IBA1) were observed. The mRNA expressions of inflammatory factors in retinas in each group were detected by real time fluorescent quantitative PCR (RT-PCR). Western blot was used to detect the phosphorylation of extracellular regulated protein kinase (ERK) and P38 in retinas. The retinal neovascularization and non-perfusion area were observed by retinal flat-mount immunofluorescence staining.Results　Immunofluorescence showed that the expression levels of Vimentin, GFAP and IBA1 in the oxygen induced group and Fpr2^-/- oxygen induced group significantly increased compared with those in the normal control group, while compared with the oxygen induced group, the expression levels of Vimentin, GFAP and IBA1 in the retina of mice in the Fpr2^-/- oxygen induced group decreased (all P<0.05). The RT-PCR results showed that, compared with the Fpr2^-/- oxygen induced group, the relative expression levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA in the retina of mice in the oxygen induced group increased (all P<0.05). The Western blot results showed that, compared with the normal control group, the relative expression levels of p-ERK1/2 and p-P38 protein in the retina of the oxygen induced group and Fpr2^-/- oxygen induced group increased, and compared with the oxygen induced group, the relative expression levels of p-ERK1/2 and p-P38 protein in the retina of the Fpr2^-/- oxygen induced group decreased (all P<0.05). Compared with the oxygen induced group, the area of neovascularization and non-perfusion area in the retina of the Fpr2^-/- oxygen induced group decreased (both P<0.05).Conclusion　Inhibition of Fpr2 can attenuate the activation of retinal glial cells, inhibit the expression of proinflammatory cytokines, and reduce ischemia-induced neovascularization in OIR mice, in which the role of the ERK and P38 signaling pathway is involved.