重组人血管内皮抑素对小鼠氧致视网膜新生血管的抑制作用

发布时间：2018-03-11 18:13

本文选题：视网膜新生血管化　切入点：血管内皮抑素　出处：《北京协和医学院》2010年博士论文　论文类型：学位论文

【摘要】：[目的]建立小鼠氧致视网膜新生血管模型,研究玻璃体腔内和腹腔内注射重组人内皮抑素(rh-ES)对视网膜新生血管的抑制作用。 [方法]将7日龄的C57BL/6小鼠连同母鼠置于氧气浓度为75%的氧箱中饲养5日后,回到空气中。对于rh-ES干预组、阳性对照组、阴性对照组的眼球,分别行玻璃体腔内注射0.04μl(0.2μg) rh-ES.0.04μl(1.0μg)贝伐单抗(Bevacizumab, Avastin)、0.04μl生理盐水(NS),病理模型组不注射,正常对照组始终饲养于空气中。5日后行右旋糖苷-异硫氰酸荧光素(FITC-dextran)灌注及视网膜整装铺片定性了解视网膜血管形态变化；制作眼球病理切片行苏木精-伊红(HE)染色,显微镜下计数突破视网膜内界膜的内皮细胞核数,定量比较各组间差异。另设置腹腔注射O.1ml(15μg) rh-ES.腹腔注射0.1ml NS两组,HE染色计数突破内界膜的内皮细胞核数,定量比较各组间差异。 [结果]与病理模型组和阴性对照组相比,rh-ES干预组视网膜铺片可见血管走行较为平直,无灌注区减少,毛细血管网络结构改善,与贝伐单抗阳性对照组作用相似；正常组视网膜突破内界膜的内皮细胞核计数为(0.2±0.15)个/张切片,rh-ES干预组(23.0±1.55)个/张切片,较病理模型组((54.6±3.10)个/张切片)明显减少(P0.01)。腹腔注射rh-ES组计数结果为(12.0±1.59)个/张切片,较阴性对照组((58.2±3.78)个/张切片)明显减少(P0.01)。 [结论]玻璃体腔内注射重组人内皮抑素可有效抑制小鼠氧致视网膜新生血管的生长；腹腔注射有效,提示全身用药是一种可能的给药方式。
[Abstract]:[objective] to establish a mouse model of retinal neovascularization induced by oxygen, and to study the inhibitory effect of recombinant human endostatin (rh-ESS) on retinal neovascularization in vitreous and intraperitoneal injection. [methods] C57BL / 6 mice of 7 days old were fed in oxygen box with oxygen concentration of 75% for 5 days and returned to the air. The eyeballs of rh-ES intervention group, positive control group and negative control group were treated. Intravitreous injection of 0.04 渭 ln (0.2 渭 g) rh-ES.0.04 渭 l (1.0 渭 g) Bevacizumaband Avastinine 0.04 渭 l of normal saline was performed respectively, and no injection was made in the pathological model group. The normal control group was kept in the air for 5 days. The rats were perfused with dextran fluorescein isothiocyanate (FITC-dextran), and the retinal vascular morphology was studied qualitatively in the retina, and the histopathological sections of the eyeball were stained with hematoxylin and eosinophore (HEH). The number of endothelial nuclei which broke through the inner boundary membrane of the retina was counted under microscope, and the differences among the groups were compared quantitatively. In addition, 0.1 ml NS was injected intraperitoneally to calculate the number of endothelial nuclei which broke through the inner boundary membrane by HE staining, and the differences among the groups were compared quantitatively. [results] compared with the pathological model group and the negative control group, the retinal stripes of the rh-ES intervention group were more straight, the no perfusion area was decreased, the capillary network structure was improved, and the effect was similar to that of the positive control group of bevacizumab. The number of endothelial cells in the normal group was 0.2 卤0.15 per slice / slice / slice, which was significantly lower than that in the pathological model group (54.6 卤3.10) / slice. The count of rh-ES was 12.0 卤1.59) per slice per slice in the intraperitoneal injection group. Compared with the negative control group (58.2 卤3.78) / sheet section, the P0.01P was decreased significantly. [conclusion] Intravitreal injection of recombinant human endostatin can effectively inhibit the growth of retinal neovascularization induced by oxygen in mice, and intraperitoneal injection is effective, suggesting that systemic administration is a possible way of administration.
【学位授予单位】：北京协和医学院
【学位级别】：博士
【学位授予年份】：2010
【分类号】：R774.1

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