奥曲肽抑制大鼠角膜新生血管形成的研究被引量：2

Inhibitory effect of octreotide on rat corneal neovascularization

下载PDF

导出

摘要目的研究奥曲肽(octreotide)对角膜新生血管(corneal neovascularization,CNV)形成的影响。方法 18只成年雌性健康SD大鼠,左眼为对照组,右眼为奥曲肽组,每组再分4、7、14d共3个时间点,每个时间点6只眼。所有大鼠双眼均通过角膜缝线法建立CNV模型,对照组术后给予生理盐水滴眼,奥曲肽组术后给予0.1mg/mL奥曲肽滴眼。显微镜下观察新生血管生长情况,免疫组织化学染色检测各时间点角膜组织中血管内皮生长因子(vascular endothelial growth factor,VEGF)和胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)的表达变化。结果奥曲肽组术后4、7、14dCNV面积均小于对照组(P<0.05),VEGF蛋白和IGF-1蛋白表达量低于对照组(P<0.05)。结论奥曲肽能下调缝线后角膜组织VEGF和IGF-1蛋白的表达,抑制CNV形成。 Objective To observe the effect of octreotide on corneal neovascularization （CNV）. Methods Totally 18 healthy adult SD rats were randomly divided into octreotide group and control group. Each group was further divided into 3 time points： 4 d, 7 d and 14 d. At each time point 6 eyes were used. All the rats were given corneal suture to induce CNV. Control group was given normal saline eye drops and octreotide group was given 0.1 mg/mL octreotide solution eye drops after surgery, 4 times daily. The occurrence and development of CNV were observed under the microscope and the expressions of vascular endothelial growth factor （VEGF） and insulin like growth factor-1 （IGF-1） proteins at each time point were detected by immunohistochemical staining. Results CNV area at postsurgical day 4, 7 and 14 was significantly smaller in octreotide group than in control group （P〈 0.05）. Expressions of VEGF and IGF-1 proteins were obviously lower in octreotide group than in control group （P〈0.05） at each time point. Oonclusion Octreotide can inhibit CNV effectively after corneal suture through down-regulating the expressions of VEGF and IGF-1 in the cornea.

作者黎彦宏张小玲耿园园

机构地区西安交通大学医学院第一附属医院眼科西安市第一医院眼科

出处《西安交通大学学报（医学版）》 CAS CSCD 北大核心 2014年第3期338-341,351,共5页 Journal of Xi’an Jiaotong University（Medical Sciences）

关键词角膜新生血管血管内皮生长因子胰岛素样生长因子-1 奥曲肽 corneal neovascularization （CNV） vascular endothelial growth factor （VEGF） insulin likegrowth factor-1 （IGF-1） octreotide

分类号 R977.1 [医药卫生—药品]

引文网络
相关文献

参考文献16

1ARBISERJL, MOSES MA, FERNANDEZ CA, et al. Oncogenic H-ras stimulates tumor angiogenesis by two distinct pathwaysJ J}. Proc Natl Acad Sci, 1997, 94(3) :861-866.
2DASGUPTA P. Somatostatin analogues: multiple roles in cellular proliferation, neoplasia, and angiogenesis[J]. Pharmacol Ther, 2004, 1020) :61-85.
3FERRARA N, HENZEL WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells[J]. Biochem Biophys Res Comrnun , 1989, 161 (2): 851- 858.
4FERRARA N , DAVIS-SMYTH T. The biology of vascular endothelial growth factor[J]. Endocr Rev, 1997, 18(1) :4-25.
5PHILIPP W, SPEICHER L, HUMPEL C. Expression of vascular endothelial growth factor and its receptors in inflamed and vascularized human corneas[J]. Invest Ophthalmol Vis Sci, 2000, 41(9) :2514-2522.
6KEATING AM,JACOBS DS. Anti-VEGF treatment of corneal neovascularization[J]. Ocul Surf, 2011, 9(4) :227-238.
7SHIG[MATSU S, YAMAUCHI K, NAKAJIMA K, et al. IGF-1 regulates migration and angiogenesis of human endothelial cells[J]. EndocrJ, 1999, 46(Suppl):S59-62.
8QIAO M, SHAPIRO P, KUMAR R, et al. Insulin-like growth factor-1 regulates endogenous RUNX2 activity in endothelial cells through a phosphatidylinositol 3-kinase/ERK-dependent and Akt-independent signaling pathway[J].J Bioi Chern , 2004,279(41):42709-42718.
9BERMONT L, LAMIELLE F, FAUCONNET S, et al. Regulation of vascular endothelial growth factor expression by insulin-like growth factor-I in endometrial adenocarcinoma cells[J]. IntJ Cancer, 2000, 850) :117-123.
10BRAZEAU P, VALE W, BURGUS R, et al. Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth horrnonclJ]. Science, 1973, 179(68) :77-79.

二级参考文献10

1Nicosia RF,Nicosia SV,Smith MS.Vascular endothelial growth factor,platelet-derived growth factor,and insulin-like growth factor-1 promote rat aortic angiogenesis in vitro[J].Am J Pathol,1994,145(5):1023-1029
2Lamberts SWJ,Lely AJ,Herder WW.Octreotide[J].N Engl J Med,1996,334(4):246-254
3Smith LEH,Wesolwski E,Mclellan A,et al.Oxygen-induced retinopathy in the mouse[J].Invest Ophthalmol Vis Sci,1994,35(1):101-111
4Danesi R,Del-Tacca M.The effects of the somatostatin analog octreotide on angiogenesis in vitro[J].Metabolism,1996,45:S49-50
5Lawnicka H,Stepien H,Wyczolkowska J,et al.Effect of somatostatin and octreotide on proliferation and vascular endothelial growth factor secretion from murine endothelial cell line (HECa10) culture[J].Biochem Biophys Res Commun,2000,268(2)∶567-571
6Murata T,Nakagawa K,Khalil A,et al.The temporal and spatial vascular endothelial growth factor expression in retinal vasculogenesis of rat neonates[J].Lab Invest,1996,74(1):68-77
7Tolentio MJ,Miller JW,Gragoudas ES,et al.Vascular endothelial growth factor is sufficient to produce iris neovascularization and neovascular glaucoma in a non-human primate[J].Arch Ophthalmol,1996,114(8):971-977
8Ozaki H,Seo MS,Ozaki K,et al.Blockade of vascular endothelial cell growth factor receptor signaling is sufficient to completely prevent retinal neovascularization[J].Am J Pathol,2000,156(2):697-707
9Smith LE,Kopchick JJ,Chen W,et al.Essential role of growth hormone in ischemia-induced retinal neovascularization[J].Science,1997,276(13):1706-1709
10Hellstrom A,Perruzzi C,Meihua J,et al.Low IGF-1 suppresses VEGF-survival signaling in retinal endothelial cells:Direct correlation with clinical retinopathy of prematurity[J].Proc Natl Acad Sci,2001,98(10)∶5804-5808