人血管内皮抑素腺病毒注射液抑制大鼠脉络膜新生血管实验研究
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上海市卫生和计划生育委员会科研课题资助项目(No.20124110)


Inhibition of the recombinant human endostatin adenavirus on experimental choroidal neovascularization in rats
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Science Foundation of Shanghai Municipal Commission of Health and Family Planning(No.20124110)

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    摘要:

    目的:探讨人血管内皮抑素腺病毒注射液(Ad-Es)玻璃体注射对半导体激光诱导的BN(Brown Norway)大鼠脉络膜新生血管(choroidal neovascularization,CNV)的抑制作用。

    方法: 雄性BN大鼠30只,右眼眼底采用激光光凝建立CNV模型,按随机数字表法分为三组:单次给药组、重复给药组及生理盐水对照组。光凝后21d,单次给药组玻璃体腔内注射Ad-Es 0.01mL; 重复给药组玻璃体腔内注射Ad-Es 0.01mL,并于1wk后重复给药; 生理盐水对照组玻璃体腔内注射生理盐水0.01mL。观察各组末次给药后7d荧光眼底血管造影荧光素渗漏情况,应用激光共焦显微镜下脉络膜血管平铺法测量各组CNV面积,光镜下观察组织细胞学变化,免疫组织化学检测CNV组织中CD105的表达。

    结果:FFA造影显示给药组渗漏发生率明显低于生理盐水对照组,重复给药组渗漏发生率低于单次给药组,差异均有统计学意义(P<0.05); 激光共焦显微镜下CNV定量分析显示给药组CNV面积显著低于对照组,重复给药组CNV面积低于单次给药组,差异均有统计学意义(P<0.05)。光镜下光凝部位新生血管内皮细胞数,给药组明显低于对照组,重复给药组低于单次给药组; CNV组织中CD105的表达,给药组明显低于生理盐水组,重复给药组低于单次给药组。

    结论:Ad-Es可以有效抑制动物模型的CNV生成,重复给药组抑制效果优于单次给药组,为治疗CNV提供了一种可能的新途径。

    Abstract:

    AIM: To investigate the inhibition of the recombinant human endostatin adenavirus(Ad-Es)on the experimental choroidal neovascularization(CNV)models by intravitreous injection.

    METHODS: Experimental CNV models were induced by semiconductor laser in 30 male Brown Norway(BN)rats and randomly divided into 3 groups with 10 rats in each group. At 21d after photocoagulation, the single administration group were given intravitreous injection with Ad-Es 0.01mL; the repeated administration group were given intravitreous injection with Ad-Es 0.01mL and a repeated injection 7d later; the saline control group were given intravitreous injection with saline 0.01mL. At 7d after final administration, the leakage of fundus fluorescein angiography(FFA)was observed. Various CNV areas were measured by using laser confocal microscopy of choroidal flatmount method. Pathology and ultrastructure were observed with light microscopy, the expressions of CD105 were measured by immunohistochemistry.

    RESULTS: The leakage of CNV of the administration group abviously decreased as compared with those in the saline group, the leakage of repeated administration group decreased compared with that of single administration group(P<0.05). Laser confocal microscope quantitative CNV analysis showed that CNV area of the administration group was significantly smaller than that of control group, the area of repeated administration group was smaller than that of single administration group(P<0.05). Under the light microscope, the vascular endothelial cell number and quantity of the administration group were significantly lower than that of the control group, the cell number of repeated administration group was lower than that of single administration group. CD105 expression of the administration group was significantly weaker than that in the saline group; the expression of repeated administration group was weaker than that of single administration group.

    CONCLUSION: Ad-Es can effectively inhibit semiconductor laser induced CNV in BN rats, and the inhibition effect of repeated administration group is better than that of single administration group. It may be a useful new method in the treatment of CNV.

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陈丽娟,宋鹤翔,苗林.人血管内皮抑素腺病毒注射液抑制大鼠脉络膜新生血管实验研究.国际眼科杂志, 2017,17(6):1037-1041.

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  • 收稿日期:2016-12-21
  • 最后修改日期:2017-05-09
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  • 在线发布日期: 2017-05-24
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