环杷明对实验性脉络膜新生血管的抑制及对Glil和HIF-1α及VEGF表达的影响  

Effects of Cyclopamine on Experimental Choroidal Neovascularization and Expression of Glil,HIF-1α and VEGF

作　　者：何花[1] 李贵刚[1] 王志涛[1] 何小阳[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院眼科,武汉430030

出　　处：《医药导报》2010年第8期980-985,共6页Herald of Medicine

基　　金：国家自然科学基金资助项目(基金编号:30901640);教育部新教师基金项目(基金编号:20090142120068);湖北省自然科学基金项目(基金编号:

摘　　要：目的探讨环杷明(cyclopamine)对实验性脉络膜新生血管的抑制机制。方法利用倍频532nm激光(140mW,75μm,0.1s)光凝方式建立BN大鼠的脉络膜新生血管(CNV)模型。光凝后立即将模型大鼠分为4组,分别为空白对照组、磷酸盐缓冲溶液(PBS)液组、环杷明2.5mg·mL-1组和环杷明4.0mg·mL-1组。除空白对照组外,各组每只眼均从光凝当天开始至光凝后13d,每隔1d分别行玻璃体腔内注射PBS5μL、2.5mg·mL-1环杷明5μL、4.0mg·mL-1环杷明5μL。激光光凝后14d行荧光素眼底血管造影和吲哚箐绿眼底血管造影观察。取眼球标本分别行FITC-右旋糖酐标记的脉络膜巩膜铺片和病理组织学观察,以检测各组处理对CNV面积和CNV中央厚度的影响。行real-timePCR检测各组处理对Shh-Gli信号级联反应和HIF-1α-VEGF信号级联反应中Glil、HIF-1α、VEGFmRNA表达的影响。结果环杷明能显著减少实验性脉络膜新生血管的形成,并呈剂量依赖关系(P<0.05);同时环杷明能明显下调Glil、HIF-1α、VEGF的mRNA表达水平(P<0.05)。结论 Shh信号通路的激活与HIF-1α-VEGF信号通路共同参与了实验性脉络膜新生血管的形成。环杷明作为Shh信号通路阻断剂能成为新的抑制CNV形成的有效药物。Objective To investigate the efficacy and mechanism of cyclopamine on experimental choroidal neovascularization （ CNV） . Methods A Brown Norway rat model of CNV was induced by laser photocoagulation （ 140 mW, 75 μm,0. 1 s） and rats were divided into blank control,PBS control and two cyclopamine treated groups （ 2. 5 mg · mL-1, 4. 0 mg·mL-1） . Except for the blank control,rats were intravitreally injected with 5 μL PBS,2. 5 mg·mL-1and 4. 0 mg·mL-1 of cyclopamine every other day,respectively,since the first day till day13 of photocoagulation. On day 14,fluorescence fundus angiography and indocyanine green eyeground angiography were carried out. The eye samples were moved out to make choroidal flatmounts marked with FITC-dextran and histologic analysis. The Sonic hedgehog （ Shh） Gli signal cascade reaction and mRNA expression level of Glil,hypoxia inducible factor （ HIF）-1α and VEGF in HIF-1α-VEGF signal cascade reaction were further analyzed by real-time PCR. Results The laser-induced rat CNV was significantly inhibited by cyclopamine（ P 0. 05） ,and which dose-dependently decreased the mRNA expression of Glil,HIF-1α and VEGF（ P 0. 05） . Conclusion The activation of Sonic hedgehog signaling pathway and HIF-1α-VEGF cascade are implicated in the development of experimental CNV. Cyclopamine as Sonic hedgehog signaling inhibitor could become a novel effective therapeutic medicine for blocking CNV formation.

关 键 词：环杷明 脉络膜新生血管 Glil 缺氧诱导因子1Α 血管内皮生长因子 

分 类 号：R988.1[医药卫生—药品]