奥曲肽抑制视网膜新生血管形成的实验研究

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。

The experimental study of octreotide suppressing retinal neovascularization

OBJECTIVE: To study the effect and therapeutically role of octreotide on retinal neovascularization. METHOD: (1) Forty one-week-old mice were randomly divided into five groups, in which four groups were exposed to 75% oxygen to establish a model of retinal neovascularization, the other group were fed in the normal environment. Mice in control group did not receive any treatment. The two experimental groups were given acetate octreotide by subcutaneous injection at the dose of 20 microg.kg(-1) and 50 microg.kg(-1) respectively twice a day for five days while the control group was given sterile PBS subcutaneously. (2) The mice were sacrificed on 17-day, the eyes were enucleated for histological examination using light and electron microscopy. (3) The effect of acetate octreotide on retinal vessels formation was assessed by counting the number of endothelial cells of new vessels extending from retina to vitreous of 4 microm sagittal retinal cross sections under the light microscope. The expression of SSTR2 in the mice retina was determined by situ hybridization. The change of retinal ultrastructure was observed under the electron microscopy. RESULTS: (1) HE staining: The numbers of endothelial cells of new vessels extending form retina to vitreous in the experimental groups were much less than the control and hyperoxia group (P < 0.01). (2) Situ hybridization showed that SSTR2 expressed in the nurtroganglion layer, endothelial cells and inner nuclear layer in the normal, control and hyperoxia group while the octreotide treated retina showed only light positive staining of SSTR2 in the nurtroganglion layer. (3) Electron microscopy showed hypoxia caused the damage of photoreceptor cells but the damage abated considerably after the mice were treated by the octreotide. CONCLUSION: Subcutaneous injection of octreotide may suppress the retinal neovascularization in the mice oxygen model and provide some of protection from the damage of retinal ultrastructure.