口服酪氨酸激酶抑制剂CM082对实验大鼠脉络膜新生血管的影响

Recent Advances in Ophthalmology(2016)

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Abstract
目的 建立脉络膜新生血管(choroidal neovascularization,CNV)大鼠模型,观察药物酪氨酸激酶抑制剂CM082对CNV的影响.方法 采用532 nm倍频激光视网膜光凝法制备棕色挪威(brown norway,BN)大鼠CNV模型.将50只光凝造模后大鼠随机分为对照组(n=25)、实验组(n=25).造模7d后给予实验组口服给药CM082 30 mg·kg-1·d-1,对照组造模后给予药物溶媒5mL· kg-1·d-1.分别于造模后7d及给药后7d、14 d行眼底荧光血管造影(fundus fluorescein angiography,FFA)、组织病理学和视网膜色素上皮(reti-nal pigment epithelium,RPE)-脉络膜-巩膜铺片进行评估.结果 FFA结果显示,实验组给药后7d、14 d光凝斑部位荧光渗漏强度(0.43 ±0.17、0.55±0.15)显著低于对照组(0.74±0.19、0.80±0.13),差异有统计学意义(P<0.05).苏木精-伊红染色的CNV病理组织学显示,实验组中病变范围较小.免疫组织化学检查表明,CM082的治疗可以明显抑制p-VEGFR-2的表达.RPE-脉络膜-巩膜铺片显示,给药后7d、14d,实验组中CNV损伤区域为(4.26±0.93)×104 μm2、(3.58±0.72)×104 μm2,明显小于对照组(12.90±6.40)×104 μm2、(17.81±5.34)×104 μm2,差异有统计学意义(P<0.05).结论 CM082口服给药30mg·kg-1·d-1能有效抑制激光诱导的BN大鼠CNV病变.
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Key words
choroidal neovascularization,tyrosine kinase inhibitor,vascular endothelial growth factor,platelet-derived growth factor
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