CXCR4抑制剂与抗血管内皮生长因子抗体联合应用对实验性脉络膜新生血管形成的干预作用

目的 观察玻璃体腔联合注射CXCR4抑制剂AMD3100与抗血管内皮生长因子(VEGF)抗体对实验性脉络膜新生血管(CNV)形成的干预作用.方法 选取48只棕色挪威(BN)大鼠随机分为AF564干预实验组(A组)、AMD3100干预实验组(B组)、联合干预实验组(C组)、磷酸盐缓冲液(PBS)对照组(D组),每组均为12只大鼠,左眼为实验眼.采用氪红激光光凝建立CNV模型.激光光凝后即刻玻璃体腔分别注射抗鼠VEGF抗体(AF564)、CXCR4特异性抑制剂AMD3100、抗鼠VEGF抗体及AMD3100、PBS各5μl.激光光凝后14 d行荧光素眼底血管造影(FFA),病理组织切片及脉络膜血管铺片检查.观察不同组别大鼠荧光渗漏程度以及CNV相对厚度和面积的变化.结果 激光光凝后14d,A、B、C、D组荧光渗漏评分分别为2.16±0.91、2.16±0.91、1.92±1.03、1.39±0.93.A、B、C组荧光渗漏较D组荧光渗漏明显受抑制,差异均有统计学意义(F=12.91,P＜0.001)；C组荧光渗漏程度低于A、B组,差异有统计学意义(F=9.21,P＜0.05).组织病理学检查显示,激光光凝后14 d,A、B、C、D组CNV相对厚度分别为1.82±0.11、1.90±0.22、1.12±0.12、2.82±0.29.A、B、C组相对CNV厚度与D组CNV相对厚度比较,差异均有统计学意义(F=5.92,P＜0.001)；C组CNV相对厚度明显变薄,与A、B组CNV相对厚度比较,差异均有统计学意义(F=5.16,P＜0.05).脉络膜血管铺片结果显示,A、B、C、D组CNV面积分别为(8204±122)、(9332±211)、(6533±101)、(13 644±255)μm2.A、B、C组CNV面积较D组CNV面积明显减少,差异均有统计学意义(F=147.50,P＜0.001)；C组CNV面积与A、B组CMV面积比较,差异有统计学意义(F=112.60,P＜0.05).结论 CXCR4抑制剂及抗VEGF抗体联合使用,可显著抑制激光诱导的CNV形成.

Inhibitory effect of CXCR4 inhibitor combined with anti-vascular endothelial growth factor antibody on experimental choroidal neovascularization

Objective To observe the effects of CXCR4 inhibitor (AMD3100) combined with antivascular endothelial growth factor (VEGF) antibody on experimental choroidal neovascularization.Methods Choroidal neovascularization (CNV) was induced in 48 Brown-Norway (BN) rats by Krypton red laser photocoagulation,and those rats were randomly divided into AF564 group (group A),AMD3100 group (group B),combined treatment group (group C) and PBS group (group D),12 rats in each group.Left eyes were the experimental eyes.The rats of group A - D received intravitreal injection of 5μl of AF564,AMD3100,AF564/AMD3100 and PBS after laser photocoagulation respectively.Fourteen days after photocoagulation,fundus fluorescein angiography (FFA),pathological section analysis and choroidal vascular wholemount were used to observe the degree of fluorescein leakage,the relative thickness and areas of CNV.Results Fourteen days after photocoagulation,the scores of fluorescein leakage in group A - D were 2.16±0.91,2.16±0.91,1.92±1.03,1.39±0.93 respectively.Fluorescein leakage in group A - C was obviously reduced compared to group D (F =12.91,P＜0.001 ),while fluorescein leakage in group C was reduced compared to group A and B (F=9.21,P＜0.05 ).The CNV relative thicknesses in group A-D were 1.82±0.11,1.90±0.22,1.12±0.12,2.82±0.29 respectively.Group A -C had thinner CNV compared to group D (F=5.92,P＜0.001),while group C had thinner CNV compared to group A and B (F=5.16,P＜0.05).The CNV areas in group A - D were (8204± 122),(9332±211),(6533± 101),and (13644±255) μm2 respectively.Group A - C had smaller CNV area compared to group D (F=147.50,P＜0.001),while group C had smaller CNV area compared to group A and B (F=112.60,P＜0.05).Conclusion Combined treatment with CXCR4 inhibitor and anti-VEGF antibody can inhibit laser-induced CNV significantly.