MMP-2和VEGF在视网膜新生血管的表达

Expression of MMP-2 and VEGF in retinal neovascularization

目的检测基质金属蛋白酶-2(matrix metalloproteinases-2,MMP-2)和血管内皮生长因子(vascular endothelial growthfactor,VEGF)在视网膜新生血管中的表达,探讨两者的相互关系。方法 取7 d龄C57BL/6J小鼠40只,随机分为高氧组和对照组,每组各20只。建立高氧诱导的视网膜新生血管小鼠模型。采用ADP酶组织化学染色、HE染色和免疫组化方法分别观察2组视网膜血管的变化、计数突破视网膜内界膜的内皮细胞核数目和检测MMP-2、VEGF的表达。结果 高氧组视网膜铺片可见大量视网膜新生血管形成,对照组未见新生血管形成;高氧组突破视网膜内界膜内皮细胞核数目为14(14.230±5.388),与对照组数目0(0.110±0.386)相比差异有统计学意义(t=23.537,P<0.001);对照组和高氧组视网膜组织中VEGF的积分光密度值分别为36.81±14.60、60.85±24.55,差异有统计学意义(t=3.348,P<0.01);对照组和高氧组视网膜组织中MMP-2的积分光密度值分别为16.33±4.13、21.12±6.29,差异有统计学意义(t=3.160,P<0.01)。高氧组视网膜组织中MMP-2和VEGF的表达呈正相关(r=0.633,P<0.01)。结论 在ROP小鼠模型的视网膜组织中,VEGF、MMP-2的表达同步升高,二者的高表达可能与视网膜新生血管形成密切相关。

Objective To investigate the correlation of matrix metalloproteinases-2 （MMP-2） with vascular endothelial growth factor （VEGF） by detecting their expression in retinal neovascularization. Methods About 40 C57BL/6J rats at postnatal 7 days were randomly divided into hyperoxia group and control group, 20 rats in each group. High oxygen induced retinal neovascularization models were established. ADP enzyme histochemical staining, HE staining and immunohistochemical method were used to detect changes of retinal vessel, number of endothelial cells breaking through retinal inner limiting membrane, expression of MMP-2 and VEGF. Results Retinal preparation could detect lots of retinal neovascularization in hyperoxia group, but not in control group. The number of nuclei from the vascular endothelial cells in the new vessels breaking through the internal limiting membrane in the hyperoxic group was 14 （ 14. 23 ± 5. 388 ）, indicating a significant increase in comparison with control group （ t = 23. 537 ,P 〈 0.001 ）. IOD of VEGF was significantly increased in the hyperoxic group to 60. 85 ±24.55 verse 36.81 ± 14.60 in the control group. There was significant difference （ t = 3. 348 ,P 〈 0, 01 ） in the level of VEGF between hyperoxic group and control group. IOD of MMP-2 significantly increased in the hyperoxic group to 21. 12 ± 6. 29 verse 16.33 ±4. 13 in the control group. There was significant difference（ t =3. 160,P 〈0.01 ） in the level of MMP-2 between hyperoxic group and control group. There was positive relationship between proteins of MMP-2 and protein of VEGF （r = 0. 533, P 〈 0.01 ）. Conclusion It suggests that the existences of VEGF and MMP-2 in the hyperoxic group correlate with retinal neovascularisation.