MIL60治疗激光诱导BN大鼠脉络膜新生血管的实验研究

发布时间：2018-02-03 20:53

本文关键词： BN大鼠脉络膜新生血管 MIL60　出处：《中国人民解放军医学院》2014年博士论文　论文类型：学位论文

【摘要】：本课题旨在采用动物实验方法,在功能、形态、细胞各个方面观察探讨MlL60对CNV的抑制作用,同时初步比较MlL60与其他常用药物对CNV的抑制作用。第一部分：532激光诱导大鼠脉络膜新生血管模型目的：应用532激光诱导技术建立BN大鼠CNV模型,观察CNV进展特点,探讨造模注意事项。方法：选取6-8周龄BN大鼠35只,分为例数相等的7个组别,其中,6组为观察组,对照组不作任何实验处理,观察组行532激光光凝,随后于不同时间点对两组FFA检查结果进行比较。结果：532激光光凝处理BN大鼠后7d可见CNV形成,14d可见CNV迅速进展,21d-28d达到峰值,28d后趋于稳定。结论：532激光光凝诱导BN大鼠CNV模型具有造模时间短,成功率高,操作简便等优势。第二部分：ML60治疗532激光诱导BN大鼠脉络膜新生血管的视网膜电图研究目的：探讨MlL60对532激光诱导BN大鼠CNV视网膜电图的影响。方法：应用ERG技术记录正常BN大鼠及玻璃体腔内注射MlL60的BN大鼠CNV模型视网膜电生理波形。结果：532激光光凝诱导BN大鼠CNV模型短期Scot-ERG表现a、b波幅值明显下降,提示视网膜内外层细胞均受到损伤；玻璃体内注射MlL60的BN大鼠CNV模型,其Scot-ERG表现b波幅值于4-6w恢复正常水平,对侧眼均未恢复正常b波幅值。结论：玻璃体内注射MlL60能够促进CNV的内层视网膜细胞修复。第三部分：MIL60抑制huvec和RPE细胞增殖迁移的实验研究目的：探讨MIL60对huvec和RPE细胞增殖和迁移能力的抑制作用。方法：采用MTT比色法及Transwell小室检测MIL60对huvec和RPE细胞增殖迁移过程的影响。结果：氪离子激光诱导BN大鼠CNV模型中可见Huvec及RPE细胞的增殖迁移,MIL60对这一过程具有抑制作用,且具有浓度依赖性。结论：VEGF在huvec及RPE细胞的增殖及迁移过程中发挥重要作用,而MIL60能够通过降低VEGF的活性抑制这一过程。第四部分ML60及其他药物对532激光诱导BN大鼠CNV的抑制作用目的：观察MIL60、Lucentis、Avastin、曲安奈德四种不同药物玻璃体内注射用于532激光诱导BN大鼠CNV模型对新生血管生长的抑制作用,初步评价MIL60用于CNV的实际疗效。方法：选取6-8周龄BN大鼠55只,随机分为6组,分别为MIL60治疗组(n=10)、Lucentis治疗组(n=10)、Avastin台疗组(n=10)、曲安奈德治疗组(n=10)、BSS注射组(n=10)、空白对照组(n=5),光凝7d后,治疗组每只大鼠玻璃体内注射5μL相应试剂,对照组仅作巩膜穿刺。于不同时间点观察FFA及CNV中央最大厚度。结果：光凝后56d,MIL60组与Avastin、Lucentis组各项指标无统计学差异,且显著优于曲安奈德组及BSS组。结论：MIL60对CNV生长过程具有强而持久的抑制作用,疗效与Avastin及Lucentis相当。
[Abstract]:The purpose of this study was to investigate the inhibitory effect of MlL60 on CNV in the aspects of function, morphology and cell. At the same time, the inhibitory effects of MlL60 and other commonly used drugs on CNV were compared. Part one: 1. Rat choroidal neovascularization model induced by 1: 532 laser Objective: to establish the CNV model of BN rats by using 532-laser induction technique, observe the progress of CNV and discuss the matters needing attention. Methods: 35 BN rats aged 6-8 weeks were selected. The patients were divided into 7 groups with equal number of cases. The observation group was treated with 532 laser photocoagulation, while the control group was treated without any experimental treatment. The results of FFA were compared between the two groups at different time points. Results the formation of CNV in BN rats was observed at 7 days after treatment with 1: 532 laser photocoagulation and the rapid progress of CNV was observed at 14 days. Conclusion the CNV model of BN rats induced by 1: 532 laser photocoagulation has the advantages of short modeling time, high success rate and easy operation. Part two: electroretinogram of choroidal neovascularization induced by 532 laser in BN rats treated with 1: ML60 Objective: to investigate the effect of MlL60 on CNV electroretinogram of BN rats induced by 532 laser. Methods:. ERG technique was used to record the retinal electrophysiological waveforms of normal BN rats and BN rats injected intravitreous with MlL60. Results:. The short-term Scot-ERG findings of BN rat CNV model induced by 532 laser photocoagulation were a. The amplitude of B wave decreased obviously, suggesting that the cells in the inner and outer layers of retina were damaged. The CNV model of BN rats with intravitreous injection of MlL60 showed that the b wave amplitude of Scot-ERG returned to normal level at 4-6 weeks. Conclusion: intravitreal injection of MlL60 can promote the repair of CNV inner retinal cells. Part three: MIL60 inhibits Proliferation and Migration of huvec and RPE cells Objective: to investigate the inhibitory effect of MIL60 on proliferation and migration of huvec and RPE cells. The effects of MIL60 on the proliferation and migration of huvec and RPE cells were detected by MTT colorimetry and Transwell chamber. Krypton laser induced proliferation and migration of Huvec and RPE cells in CNV model of BN rats. Conclusion MIL60 plays an important role in the proliferation and migration of huvec and RPE cells. MIL60 can inhibit this process by reducing the activity of VEGF. Inhibitory effects of 4th partial ML60 and other drugs on CNV induced by 532 Laser in BN Rats Objective: to observe the Avastin of Lucentism in MIL60. Effects of intravitreal injection of triamcinolone acetonide on angiogenesis in BN rats induced by 532 laser. Methods: 55 BN rats aged 6-8 weeks were randomly divided into 6 groups: MIL60 treatment group (n = 10). The Lucentis treatment group was treated with Avastin, and the triamcinolone acetonide treatment group was treated with triamcinolone acetonide. After 7 days of photocoagulation, 5 渭 L corresponding reagents were injected into the vitreous of each rat in the treatment group. In the control group, scleral puncture was performed only. The maximum central thickness of FFA and CNV was observed at different time points. Results: MIL60 group and Avastin group were observed at 56 days after photocoagulation. There was no statistical difference in the indexes of Lucentis group, and it was significantly better than that of triamcinolone acetonide group and BSS group. Conclusion: 1 MIL60 has a strong and lasting inhibitory effect on the growth of CNV. The efficacy was comparable to that of Avastin and Lucentis.
【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R773.4

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