Zou Yanhong, Xu Xinrong, Chiou George C Y
Institute of Ocular Pharmacology, Medical Pharmacology & Toxicology, College of Medicine, Texas A&M University System Health Science Center, College Station, TX 77843, USA.
J Ocul Pharmacol Ther. 2006 Feb;22(1):19-25. doi: 10.1089/jop.2006.22.19.
The aim of this study was to investigate the effect of interleukin-1 blockers, CK112 and CK116, on laser-induced experimental choroidal neovascularization (CNV) in rat models in vivo and endothelial cell proliferation in vitro.
Male Brown Norway rats were anesthetized to receive Nd:YAG laser to break the Bruch's membrane. CK112, CK116, and prednisolone were given once-daily through intraperitoneal (i.p.) injection after laser treatment for 4 weeks. The development of CNV was determined by fluorescein angiography performed on weeks 2 and 4. Human umbilical vein endothelial cells (HUVEC) were tested with proliferation assay with CK112, CK116, and prednisolone at different concentrations.
The intensity of fluorescein leakage from the photocoagulated lesions decreased significantly, compared to the control group (treated with dimethyl sulfoxide [DMSO] only), following CK112, CK116, and prednisolone treatment. Four (4) weeks after administration, CK112, at 10 mg/kg and 30 mg/kg, inhibited CNV development to 75% and 77% of the control group, respectively (P < 0.01). Both CK116, 10 mg/kg, and prednisolone, 5 mg/kg, inhibited the CNV development to 85% of the control group (P < 0.05). All three compounds interfered with the endothelial cell proliferation significantly. The reduction of the endothelial cells was 50.5% (P < 0.01), 28.5% (P < 0.05), and 23.1% (P < 0.05), respectively, in 500 microg/mL, 300 microg/mL, and 100 microg/mL of the CK112-treated group. CK116 inhibited the cell proliferation significantly to 77.2% of the control group at 500 microg/mL (P < 0.05).
CK112 and CK116 inhibited the development of CNV in the rat model and interfered with vascular endothelial cell proliferation in vitro. Our results suggest that CK112 and CK116 may be good candidates to inhibit ocular neovascularization related to age-related macular degeneration (ARMD).
本研究旨在探讨白细胞介素 -1 阻滞剂 CK112 和 CK116 对大鼠体内激光诱导的实验性脉络膜新生血管形成（CNV）以及体外内皮细胞增殖的影响。
对雄性挪威棕色大鼠进行麻醉，接受 Nd:YAG 激光以破坏 Bruch 膜。激光治疗后 4 周，通过腹腔内（i.p.）注射，每天给予一次 CK112、CK116 和泼尼松龙。在第 2 周和第 4 周进行荧光素血管造影以确定 CNV 的发展情况。用不同浓度的 CK112、CK116 和泼尼松龙对人脐静脉内皮细胞（HUVEC）进行增殖测定。
与对照组（仅用二甲基亚砜 [DMSO] 处理）相比，CK112、CK116 和泼尼松龙处理后，光凝损伤处的荧光素渗漏强度显著降低。给药 4 周后，10 mg/kg 和 30 mg/kg 的 CK112 分别将 CNV 发展抑制至对照组的 75%和 77%（P < 0.01）。10 mg/kg 的 CK116 和 5 mg/kg 的泼尼松龙均将 CNV 发展抑制至对照组的 85%（P < 0.05）。所有三种化合物均显著干扰内皮细胞增殖。在 500 μg/mL、300 μg/mL 和 100 μg/mL 的 CK112 处理组中，内皮细胞减少分别为 50.5%（P < 0.01）、28.5%（P < 0.05）和 23.1%（P < 0.05）。500 μg/mL 的 CK116 显著抑制细胞增殖至对照组的 77.2%（P < 0.05）。
CK112 和 CK116 在大鼠模型中抑制了 CNV 的发展，并在体外干扰了血管内皮细胞增殖。我们的结果表明，CK112 和 CK116 可能是抑制与年龄相关性黄斑变性（ARMD）相关的眼部新生血管形成的良好候选药物。
