柚皮素磷脂复合物对实验性脉络膜新生血管形成的抑制作用及其机制研究  

Study on the inhibitory effect and its mechanisms of Naringin phospholipid complex on experimental choroidal neovascularization

作　　者：朱寅 荣飞 沈毅飞 ZHU Yin;RONG Fei;SHEN Yi-fei(Department of Ophthalmology,The First People's Hospital of Wujiang District in Suzhou,Suzhou 215200,Jiangsu Province,China)

机构地区：[1]苏州市吴江区第一人民医院眼科

出　　处：《中国临床药理学杂志》2019年第20期2593-2596,共4页The Chinese Journal of Clinical Pharmacology

基　　金：江苏省医药卫生基金资助项目(YGZXZ1511)

摘　　要：目的探讨柚皮素磷脂复合物(NPC)对实验性脉络膜新生血管的抑制作用及对基质细胞衍生因子-1(SDF-1)/CXC趋化因子受体4(CXCR4)通路的影响。方法用氪激光光凝视网膜与脉络膜法制备脉络膜新生血管大鼠。按照体重将大鼠随机6组:正常组(0.9% NaCl)、模型组(建模后0.9% NaCl)、对照组(柚皮素20mg·kg^-1)和低、中、高3个剂量实验组(柚皮素磷脂复合物30,60,90mg·mL^-1),每组20只。分别用实时荧光定量PCR和免疫组化检测脉络膜中SDF-1、CXCR4的基因和蛋白表达水平;用免疫印迹法检测血管内皮生长因子(VEGF)、基质金属蛋白酶2(MMP-2)和基质金属蛋白酶9(MMP-9)蛋白表达水平。结果给药后,模型组、对照组和高剂量实验组的SDF-1基因表达水平分别为1.94±0.12,1.62±0.11和1.06±0.09;上述这3组的SDF-1蛋白表达水平分别为57.42±5.67,47.54±4.06和30.28±4.06;上述这3组的CXCR4基因表达水平分别为1.84±0.06,1.38±0.07和1.07±0.05,上述这3组的CXCR4蛋白表达水平为70.44±4.59,60.34±4.36和45.18±4.09;上述这3组的的VEGF分别为1.16±0.06,0.79±0.07和0.31±0.05;上述这3组的MMP-2分别为1.20±0.07,0.65±0.09和0.47±0.08;上述这3组的MMP-9分别为1.47±0.05,1.13±0.06和0.33±0.04。高实验剂量组和对照组与模型组比较,差异均有统计学意义(P<0.05)。结论NPC能够抑制实验性脉络膜新生血管形成,其机制可能与抑制SDF-1/CXCR4通路和影响VEGF、MMP-2与MMP-9蛋白表达有关。Objective To investigate the inhibitory effect of Naringin phospholipid complex(NPC)on experimental choroidal neovascularization and its influence on stromal cell derived factor-1(SDF-1)/CXC chemokine receptor 4(CXCR4)pathway.Methods Choroidal neovascularization in rats was prepared by krypton laser photocoagulation of retina and choroid.Rats were randomly divided into six groups:normal group(saline),model group(saline after modeling),control group(naringin20 mg·kg^-1),experimental-L,-M,-H groups(NPC 30,60,90 mg·m L^-1),20 rats in each group.The expressions of stromal cell derived factor-1(SDF-1)and chemokine receptor 4(CXCR4)m RNA and its protein in choroid were detected by real-time fluorescence quantitative PCR and immunohistochemistry,respectively.The expression of vascular endothelial growth factor(VEGF),matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9)protein were detected by immunoblotting.Results After administration,SDF-1 gene expression in model group,control group and experimental-H group respectively were 1.94±0.12,1.62±0.11,1.06±0.09;the SDF-1 proteins expression in the above three groups were 57.42±5.67,47.54±4.06,30.28±4.06;the CXCR4 m RNA in the above three groups were1.84±0.06,1.38±0.07,1.07±0.05,and the CXCR4 proteins in the above three groups were 70.44±4.59,60.34±4.36,45.18±4.09;the levels of VEGF in the above three groups were 1.16±0.06,0.79±0.07,0.31±0.05;the levels of MMP-2 in the above three groups were 1.20±0.07,0.65±0.09,0.47±0.08;the levels of MMP-9 in the above three groups were 1.47±0.05,1.13±0.06,0.33±0.04.There were significant differences between the experimental-H group and control group with model group(all P<0.05).Conclusion NPC can inhibit the formation of experimental choroidal neovascularization,the mechanism may be related to inhibiting the SDF-1/CXCR4 pathway and affecting the expressions of VEGF,MMP-2 and MMP-9.

关 键 词：实验性脉络膜新生血管 柚皮素磷脂复合物 基质细胞衍生因子-1 趋化因子受体4 

分 类 号：R28[医药卫生—中药学]