摘要
目的探讨人血管内皮抑素腺病毒(Ad-Es)注射液对半导体激光诱导的BN大鼠脉络膜新生血管(CNV)的抑制作用。并比较不同给药方式的治疗效果,从而明确药物疗效及最佳给药途径,为进一步基因治疗临床试验奠定基础。方法雄性BN大鼠40只,右眼眼底采用半导体激光光凝方式建立CNV模型,随机分为4组,每组10只(10只眼)。光凝后21 d,A组于玻璃体腔内注射Ad-Es 0.01 mL;B组于球周注射Ad-Es 0.01 mL;C组于玻璃体腔内注射生理盐水0.01 mL;D组于球周注射生理盐水0.01 mL。观察给药后7 d各组的荧光眼底血管造影(FFA)荧光素渗漏情况,应用激光共焦显微镜下脉络膜血管平铺法测量各组CNV面积,光镜下观察组织细胞学变化,免疫组化检测CD105的表达。结果FFA晚期图像A组和B组视网膜光凝斑荧光素渗漏得到明显抑制,A组抑制效果更强;激光共焦显微镜下观察CNV面积,A组和B组CNV面积显著低于C、D组,A组CNV面积低于B组;组织病理学观察显示C、D组光凝区纤维血管较A、B组明显增多,A组低于B组;A、B组CNV相关表达因子CD105表达下降,A组较B组表达下降更明显。结论 Ad-Es注射液可以有效抑制动物模型的CNV表达,玻璃体腔注射给药抑制效果优于球周注射给药,为治疗CNV提供了一种新的可能途径。
Objective To investigate the inhibition of recombinant human endostatin adenavirus （Ad-Es） on the ex- perimental choroidal neovascularization （CNV） model induced by semiconductor laser photocoagulation. Methods Experimental CNV model was induced by semiconductor laser in 40 male Brown Norway （BN） rats （40 eyes） and randomly divided into 4 groups with 10 rats （10 eyes） in each group. Twenty-one days after the photocoagulation, group A were given intravitreal injection with Ad-Es 0.01 mL; group B were given periocular injection with Ad-Es 0.01 mL; group C were given intravitreal injection with saline 0.01 mL; and group D were given periocular injection with saline 0.01 mL. We observed the intensity of fundus fluorescein angiography （FFA） leakage 7 days after the administration. Various CNV areas were measured with laser confocal microscopy of choroidal flatmount method. The pathology and ultrastrueture were observed with light microscopy, and the expression of CD105 was measured by immunohistochemical method. Results The leakage of CNV in group A and B was abviously decreased as compared with that in group C and D, and the leakage of group A was decreased more than that of group B （P 〈 0.05）. Laser confocal microscope quantitative CNV analysis showed that CNV area of group A and B was significantly smaller than that of the control groups, and the area of group A was smaller than that of group B （P 〈 0.05）. Under the light microscope, the vascular endothelial cell number and quantity of group A and B were sig- nificantly lower than those of group C and D, and the cell number of group A was lower than that of group B. The CD105 expression of group A and group B was significantly weaker than that in group C and group D, with group A weaker than group B. Conclusion Ad-Es can effectively inhibit semiconductor induced CNV in BN rats, and the inhibition effect in the intravitreal injection group is stronger than that in the periocular injection group, which may be a new method in the tr
出处
《中南药学》
CAS
2017年第7期889-893,共5页
Central South Pharmacy
基金
上海市卫生局面上项目(编号:20124110)
