本文選題：視網(wǎng)膜新生血管化　切入點：血管內(nèi)皮抑素　出處：《北京協(xié)和醫(yī)學院》2010年博士論文　論文類型：學位論文

【摘要】：[目的]建立小鼠氧致視網(wǎng)膜新生血管模型,研究玻璃體腔內(nèi)和腹腔內(nèi)注射重組人內(nèi)皮抑素(rh-ES)對視網(wǎng)膜新生血管的抑制作用。 [方法]將7日齡的C57BL/6小鼠連同母鼠置于氧氣濃度為75%的氧箱中飼養(yǎng)5日后,回到空氣中。對于rh-ES干預(yù)組、陽性對照組、陰性對照組的眼球,分別行玻璃體腔內(nèi)注射0.04μl(0.2μg) rh-ES.0.04μl(1.0μg)貝伐單抗(Bevacizumab, Avastin)、0.04μl生理鹽水(NS),病理模型組不注射,正常對照組始終飼養(yǎng)于空氣中。5日后行右旋糖苷-異硫氰酸熒光素(FITC-dextran)灌注及視網(wǎng)膜整裝鋪片定性了解視網(wǎng)膜血管形態(tài)變化；制作眼球病理切片行蘇木精-伊紅(HE)染色,顯微鏡下計數(shù)突破視網(wǎng)膜內(nèi)界膜的內(nèi)皮細胞核數(shù),定量比較各組間差異。另設(shè)置腹腔注射O.1ml(15μg) rh-ES.腹腔注射0.1ml NS兩組,HE染色計數(shù)突破內(nèi)界膜的內(nèi)皮細胞核數(shù),定量比較各組間差異。 [結(jié)果]與病理模型組和陰性對照組相比,rh-ES干預(yù)組視網(wǎng)膜鋪片可見血管走行較為平直,無灌注區(qū)減少,毛細血管網(wǎng)絡(luò)結(jié)構(gòu)改善,與貝伐單抗陽性對照組作用相似；正常組視網(wǎng)膜突破內(nèi)界膜的內(nèi)皮細胞核計數(shù)為(0.2±0.15)個/張切片,rh-ES干預(yù)組(23.0±1.55)個/張切片,較病理模型組((54.6±3.10)個/張切片)明顯減少(P0.01)。腹腔注射rh-ES組計數(shù)結(jié)果為(12.0±1.59)個/張切片,較陰性對照組((58.2±3.78)個/張切片)明顯減少(P0.01)。 [結(jié)論]玻璃體腔內(nèi)注射重組人內(nèi)皮抑素可有效抑制小鼠氧致視網(wǎng)膜新生血管的生長；腹腔注射有效,提示全身用藥是一種可能的給藥方式。
[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 鹵0.15 per slice / slice / slice, which was significantly lower than that in the pathological model group (54.6 鹵3.10) / slice. The count of rh-ES was 12.0 鹵1.59) per slice per slice in the intraperitoneal injection group. Compared with the negative control group (58.2 鹵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.
【學位授予單位】：北京協(xié)和醫(yī)學院
【學位級別】：博士
【學位授予年份】：2010
【分類號】：R774.1

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