摘要
目的观察选择性环氧化酶-2（COX-2）抑制剂塞来昔布（celecoxib）对实验性脉络膜新生血管（CNV）的抑制作用。方法鼠龄8～10周的健康雄性棕色挪威（BN）大鼠30只，随机分为空白对照组、实验对照组和塞来昔布治疗组，每组10只。塞来昔布治疗组采用灌胃法给药，剂量50mg／kg，2次／d。给药后7d，采用氪激光建立大鼠CNV模型，分别于激光光凝后3、7、14、21、30d对实验对照组和塞来昔布治疗组所有大鼠行荧光素眼底血管造影（FFA）检查。激光光凝后21d，每组随机处死5只大鼠，摘除眼球，制作空白对照组球后段组织切片、实验对照组和治疗组CNV膜切片。常规苏木精伊红（HE）染色，计算实验对照组和塞来昔布治疗组的CNV膜相对厚度；采用免疫组织化学方法检测COX-2、血管内皮生长因子（VEGF）及基质金属蛋白酶-2（MMP-2）的表达。结果激光光凝后21d，塞来昔布治疗组CNV发生率明显低于实验对照组（X^2=7．1068，P=0．0077），CNV相对厚度较实验对照组明显减少（t=16．7600，P=0．000O），COX-2、vEGF和MMP-2在CNV膜上的阳性表达均明显低于实验对照组（t=5．7100，5．8400，8．0200；P=0．000O）；空白对照组大鼠COX-2、VEGF和MMP-2在视网膜和脉络膜中的表达非常弱。结论预防性服用塞来昔布能抑制激光诱导CNV的发生；通过抑制COX-2可减少CNV中VEGF和MMP-2的表达。
Objective To observe the inhibition effect of selective cyclooxygenase-2 inhibitor （celecoxib） on the experimental choroidal neovascularization （CNV）. Methods Thirty 8-10 weeks old healthy male Brown-Norway（BN）rats were randomly divided into the control, laser and celecoxib group, with 10 rats in each group. At the dosage of 50 mg/kg, celecoxib was gavaged twice per day. After 7 days, experimental CNV was induced by Krypon laser on laser group and eelecoxib group. Fundus fluorescein angiograpby （FFA） was performed on days 3, 7, 14, 21, 30 after laser photocoagulation. On days 21 after photocoagulation, 5 rats in each group were sacrificed and the relative thickness of CNV membranes, the expression of COX-2, vascular endothelial growth factor（VEGF） and matrix metalloproteinase-2 （MMP-2） Were studied by histopathologic or immunohistochemistry examination. Results On days 21 after photocoagulation, the incidence of CNV in the celecoxib group is significantly lower than that in the laser group （X^2= 7. 1068, P= 0v0077） ; the relative thickness of the CNV membranes in the eelecoxib group is reduced 41.38% compared to the laser group, the difference is statistically significant （t= 16. 7600,P= 0. 0000）. COX-2, VEGF and MMP-2 expression in the CNV membrane of celecoxib group were significantly lower than in control group （t= 5. 7100, 5. 8400, 8. 0200; P= 0. 0000） ; the COX-2, VEGF and MMP-2 expressions in choroid and retina of control group were weak. Conclusion Prophylactic celecoxib can reduce the expression of VEGF and MMP-2 by inhibiting COX-2, and prevent the CNV induced by laser pbotocoagulation.
出处
《中华眼底病杂志》
CAS
CSCD
北大核心
2010年第1期32-36,共5页
Chinese Journal of Ocular Fundus Diseases
基金
河北省卫生厅资助项目（2007029）
