抗血管内皮生长因子单克隆抗体bevacizumab抑制大鼠脉络膜新生血管
Experimental study on the inhibitory effect of bevacizumab on choroidal neovascularization in rat
摘要目的 观察玻璃体腔注射抗血管内皮生长因子(VEGF)单克隆抗体bevacizumab(商品名Avastin)抑制激光诱导的实验性脉络膜新生血管(CNV)的效果及特点.方法 12只雄性棕色挪威(BN)大鼠平均分为bevacizumab组和对照组,每组6只.每一只大鼠随机选取1只眼为实验眼,采用半导体激光围绕其视盘激光光凝8点后,bevacizumab组和对照组玻璃体腔立即分别给予2.00 μl bevacizumab和乳酸林格注射液.激光光凝后7、14、21 d两组行荧光素跟底血管造影(FFA)和吲哚青绿血管造影(ICGA)动态观察CNV的形态及渗漏情况.激光光凝后21 d摘除实验眼作石蜡切片行苏木精-伊红染色,比较两组CNV的高度,同时行VEGF免疫组织化学染色,观察CNV斑块中VEGF的表达情况.结果 激光光凝后7 d,ICGA检查结果显示,bevacizumab组和对照组均有CNV生成.FFA检查结果显示,bevacizumab组的渗漏强度始终比对照组弱,但bevacizumab组渗漏强度随时间推移逐渐增强.bevacizumab组CNV平均厚度比对照组低.免疫组织化学检查结果显示,bevacizumab组VEGF表达阴性.结论 激光光凝后立即玻璃体腔注射2.00 μl bevacizumab可以降低CNV厚度并抑制其渗漏,但不能阻止CNV的生成,抑制CNV渗漏的效果不能长时间保持.
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abstractsObjective To observe the inhibitory effects and characteristics of intravitreal injection with bevacizumab on laser-induced choroidal neovascularization (CNV).Methods Twelve male brown norway (BN) rats were divided into the bevacizumab group and control group with six rats in each group.One eye of rats were received a series of 8 diode laser esions around optic disc to induce CNV,then the rats in bevacizumab group and control group underwent intravitreal injection with 2 μl bevacizumab and ringer's lactate.On days 7,14,and 21,the morphology and leakage of CNV were observed by fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA).On day 21 after photocoagulation,thephotocoagulated eyes were enucleated and processed for histopathologie examination,including hematoxylin and eosin (H&E) staining and immunohistochemistry staining for vascular endothelial growth factor (VEGF).Results On day 7 after photocoagulation,ICGA showed that CNV developed in the bevacizumab group and the control group.FFA showed that leakage intensity in the bevacizumab group was significantly lower than that in the control group,but the bevacizumab group gradually increased over time.The mean thickness of CNV significantly decreased in the bevacizumab group.The CNV in the bevacizumab group were negative for VEGF according to the result of immmuohistochemistry staining.Conclusions Early intravitreal injection with 2 μl bevacizumab can reduce the thickness of CNV and inhibit the leakage of CNV.However,bevacizumab could neither block the formation of CNV,nor suppress the permeability permanently.Combined other therapies with bevacizumab may be more potential to treat CNV effectively.
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