柚皮素铜、锌配合物的制备及其对大鼠实验性脉络膜新生血管的抑制作用
Synthesis of Naringenin Complexes with Cu and Zn and the Inhibiting Effects on Experimental Choroidal Neovascularization in Rats
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摘要: 目的 制备柚皮素铜、锌配合物，比较配合物与柚皮素对大鼠激光诱发脉络膜新生血管(CNV)的抑制作用。方法 以柚皮素为配体与铜、锌金属离子分别在甲醇、乙醇溶液中配位，合成柚皮素铜、锌配合物，对配合物进行元素分析，利用红外、紫外光谱对配合物进行表征。采用氪激光制作大鼠CNV模型，模型动物随机分为溶媒对照组、柚皮素组及柚皮素铜、锌配合物4组，每组5只。视网膜光凝后开始给药，给药剂量：20 mg/(kg·d)，溶媒对照组给等体积的二甲基亚砜（DMSO）。腹腔注射给药，每日1次，连续4周。给药后4周进行荧光素异硫氰酸酯葡聚糖(FITC-D)食下静脉注射，用脉络膜铺片法测量CNV面积。结果 柚皮素与铜、锌金属离子形成了稳定的配合物。实验动物CNV面积（×103）测定：溶媒对照组（34.56±1.67）μm2、柚皮素组（20.90±1.47）μm2、柚皮素铜配合物组（13.24±1.33）μm2、柚皮素锌配合物组（13.0±1.28）μm2。柚皮素及其铜、锌配合物组CNV面积明显小于溶媒对照组(P<0.05，P<0.01)，柚皮素铜、锌配合物组则小于柚皮素组，(P<0.05)。结论 柚皮素与铜、锌金属离子形成配合物后，生物活性显著增加，抑制模型大鼠CNV的作用强于柚皮素。
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关键词:
- 柚皮素 /
- 铜、锌配合物 /
- 实验性脉络膜新生血管
Abstract: OBJECTIVE To compare the inhibiting effects of naringenin complexes with Cu and Zn with free ligand on laser-induced choroidal neovascularization (CNV) in rats. METHODS Naringenin complexes with Cu and Zn have been synthesized and characterized on the basis of elemental analyses， i.r. spectra， u.v. spectra. Male Brown Norway rats were anesthetized to receive krypton laser to induce CNV. 20 model rats were divided randomly into control， naringenin complexes with Cu and Zn groups， 5 rats in each group. Naringenin and its complexes (20mg/kg/d )were given once-daily through intraperitoneal (i.p.) injection after laser treatment for 4 weeks. The sizes of CNV lesions were measured by choroidal flatmounts with fluorescein isothiocyanate dextran for four weeks. RESULTS The animals treated with naringenin complexes with Cu and Zn showed significant decrease in their average CNV sizes (20.90±1.47)×103μm2， (13.24±1.33)×103μm2， (13.0±1.28)×103μm2， compared with the vehicle-treated animals (34.56±1.67)×103μm2， P<0.05 and <0.01 respectively. Furthermore， naringenin complexes with Cu and Zn reduce the CNV size even more than naringenin (P<0.05 ) . CONCLUSION These results indicate that the biological activity of naringenin can be enhanced by the formation of complexes with Cu and Zn， and complexes of naringenin have stronger inhibition on CNV in the rat model than that of free ligand . -
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