抗血管内皮生长因子单克隆抗体Bevacizumab抑制氧致视网膜病变模型鼠新生血管

目的观察抗血管内皮生长因子单克隆抗体Bevacizumab 对氧致视网膜病变模型鼠视网膜新生血管的抑制作用。方法7日龄C57BL/6J幼鼠90只，数字表法随机分为4组：1 组15只，为正常对照组；2组15只，为给氧对照组；3组30只，为大剂量Bevacizumab治疗组 ；4组30只，为小剂量Bevacizumab治疗组。其中，2、3、4组置于氧浓度（75±2）%的容器内连续饲养至12日龄，再置于正常空气下饲养。第12天3、4组幼鼠玻璃体腔分别注射Bevacizumab 2、1 μl，对侧眼注射相同体积的平衡盐溶液作为对照。二磷酸腺苷酶染色法进行 视网膜铺片,了解视网膜血管改变；视网膜切片染色，计数小鼠视网膜新生血管内皮细胞核数；逆转录聚合酶链反应（RT-PCR）检测血管内皮生长因子（VEGF） mRNA的表达。结果与给氧对照组比较, Bevacizumab治疗组视网膜血管分布规则、密度减少,突破视网膜内界膜的内皮细胞核数目明显减少(P＜0.001),但不同剂量治疗组间比较，差异无统计学意义 (P＞0.05) ；给氧组无论是否采用Bevacizumab治疗，也不论Bevacizumab剂量大小，其VEGF的mRNA表达 量比较，差异均无统计学意义（P＞0.05）。结论抗VEGF单克隆抗体Bevacizumab能有效抑制氧致视网膜病变模型鼠视网膜新生血管的形成，可能成为治疗氧致视网膜病变等早产儿视网膜病变的一种新方法。（中华眼底病杂志，2008，24：184-188）

The inhibitory effect of Bevacizumab on retinal neovascularization in oxygen-induced retinopathy in the mouse

Objective To observe the inhibitory effect of Bevacizumab on retinal neovascularization in oxygen-induced retinopathy in the mouse. Methods 90 one-week-old C57BL/6J mice were divided into four groups at random.15 mice in the 1st group as normal control group,15 mice in the 2nd group as oxygen control group,30 mice in the 3rd group as high-dose Bevacizumab treatment group,30 mice in the 4th group as low-dose Bevacizumab treatment group.The 2nd,3rd and 4th groups were exposed to 75%oxygen for 5 days and then to room air.At the 12th day,One eye of each mouse of two control groups were received an intravitreal injection with Bevacizumab at 2μl、1μl respectively,and the same volume of BSS was injected into the other eye of the mice.The adenosine diphosphatase(ADPase)histochemical technique was used for retinal flat mount to assess the oxygen-induced changes of retinal vessels.The number of the endothelium cell nuclei of proliferative neovascularization was quantified by retinal microtome chromoscopy.Real-time PCR analysis was performed to examine the expression of VEGF mRNA. Results Comparing with oxygen control group,regular distributions,reduced density of retinal vascular and reduced endothelium cell nuclei which extending retinal membrane were observed in the treatment groups(P＜0.001).But the differences between two treatment groups are not statistically significant(P＞0.05).The expression of VEGF mRNA was not significantly different in oxygen control group whatever it whether accepted Bevacizumab treatment or high or low dose(P＞0.05). Conclusion Intravitreal injection with Bevacizumab can effectively inhibits the retinal neovascularization in oxygeninduced retinopathy in the mouse.Intravitreal injection with Bevacizumab might become to the new method to treat retinopathy of premature.