奥曲肽抑制视网膜新生血管形成的实验研究

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目的 探讨生长抑素类似物奥曲肽对视网膜新生血管形成的影响及其治疗作用。方法 将鼠龄7d的小鼠40只随机分为5组,每组8只。正常对照组于正常空气环境中饲养,不予任何处理;其他4组置于氧箱中饲养。实验组分别皮下注射奥曲肽20和50μg·kg-1·d-1,实验对照组皮下注射等量PBS,连续用药5d,高氧组不注射奥曲肽。将鼠龄17d的小鼠处死,摘除眼球制作标本,进行组织病理学及电镜观察。光镜下观察并计数突破视网膜内界膜的血管内皮细胞核数。原位杂交法检测生长抑素受体2(SSTR2)在视网膜上的表达。电镜下观察视网膜组织超微结构的改变。结果 正常对照组标本HE染色几乎未见突破内界膜的血管内皮细胞核,高氧组和实验对照组可见较多的突破内界膜的血管内皮细胞核,而实验组的数目明显少于高氧组和实验对照组。SSTR2原位杂交染色可见正常对照组、高氧组、实验对照组视网膜神经节细胞层、内核层及血管内皮细胞SSTR2强阳性表达,实验组呈弱阳性表达,其中大剂量实验组的表达更弱于小剂量实验组。电镜下可见缺氧引起小鼠视网膜视细胞层的破坏,奥曲肽治疗后,视网膜超微结构的损害明显好转。结论 奥曲肽能有效抑制视网膜新生血管的形成,在一定程度上可预防缺氧造成的视网膜超微结构的损害。 Objective To investigate the effect of somatostatin analogue octreotide on retinal neovascularization and its therapeutic effect. Methods 40 mice of 7 days old were randomly divided into 5 groups with 8 mice in each group. The normal control group was kept in normal air environment without any treatment; the other 4 groups were housed in oxygen box. The experimental group were injected subcutaneously with octreotide 20 and 50 μg · kg-1 · d-1, respectively, and the experimental control group was subcutaneously injected with PBS in equal volume for 5 days. Oxytocin was not injected in the hyperoxia group. The mice at the age of 17 days were sacrificed and their eyes were removed to make specimens for histopathology and electron microscopy. Light microscope and count the number of breakthrough in the inner limiting membrane of the vascular endothelial cell nucleus. In situ hybridization was used to detect the expression of somatostatin receptor 2 (SSTR2) on the retina. The ultrastructural changes of retina were observed under electron microscope. Results There were almost no vascular endothelial nuclei that broke through the internal limiting membrane in HE staining of normal control group. Vascular endothelial nuclei that broke through the internal limiting membrane were found in hyperoxia group and experimental control group, while the number of experimental group was significantly less than that in hyperoxia group And experimental control group. SSTR2 staining in situ hybridization showed that the normal control group, hyperoxia group, experimental control group retinal ganglion cell layer, the inner nuclear layer and vascular endothelial cells SSTR2 strong positive expression in the experimental group was weakly positive expression in which the high-dose experimental group was weaker expression In the low-dose experimental group. Electron microscopy shows hypoxia-induced destruction of the retinal layer of the mouse retina, octreotide treatment, retinal ultrastructure damage was significantly improved. Conclusion Octreotide can effectively inhibit the formation of retinal neovascularization, which can prevent the damage of retinal ultrastructure caused by hypoxia to a certain extent.
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