探讨酪氨酸激酶抑制剂E7080对实验大鼠脉络膜新生血管(CNV)的抑制作用。

成年雄性棕色挪威大鼠60只，由北京维通利华实验动物公司提供。采用数字表法将大鼠随机分为对照组、E7080低剂量组(10 mg·kg^-1·d^-1)及E7080高剂量组(20 mg·kg^-1·d^-1)，每组各20只。采用激光诱导实验大鼠形成CNV，以完成动物模型的制作。7 d后，按不同分组给药干预。分别于造模后7 d及给药后7 d、14 d采用荧光素眼底血管造影检查CNV形成与荧光渗漏的情况。分别于给药后7 d和14 d，采用组织病理学的方法评估CNV的病理情况。分别于造模后7 d及给药后14 d，采用视网膜色素上皮层-脉络膜-巩膜复合体铺片植物凝集素B4染色观察CNV的面积。CNV荧光信号的强度、CNV荧光信号的厚度以及凝集素B4染色的CNV面积，以均数±标准差进行描述。多组样本间不同组间均数的比较，采用重复测量资料的方差分析，采用LSD检验进行两两比较。

荧光素眼底血管造影的检查结果显示，给药7 d后，低剂量组和高剂量组实验大鼠CNV相对渗漏荧光信号的强度分别为(0.5378±0.0967)和(0.3774±0.086)，均低于对照组的(0.6752±0.095)，差异具有统计学意义(t＝6.342，13.99；P<0.05)；给药14 d后，低剂量组和高剂量组的CNV相对渗漏荧光信号强度分别为(0.5735±0.0726)和(0.4071±0.1197)，也均低于对照组(0.7305±0.0924)，差异有统计学意义(t＝6.92，14.50；P<0.05)。苏木精-伊红染色结果显示，药物处理7 d后，低剂量组和高剂量组的CNV厚度分别为(84.14±8.829)μm和(77.23±9.365)μm，均低于对照组的(125.3±18.18)μm，差异具有统计学意义(t＝7.38，8.628；P<0.05)；药物处理14 d后，低剂量组和高剂量组的CNV厚度分别为(86.21±10.51)μm和(77.88±7.39)μm，均低于对照组的(147.9±19.66)μm，差异具有统计学意义(t＝9.656，10.44；P<0.05)。视网膜色素上皮层-脉络膜-巩膜复合体铺片荧光染色显示，低剂量组和高剂量组实验大鼠CNV的平均面积分别为(18 991±8665)μm²和(20 083±11 759)μm²，均低于对照组的(51 156±24 348)μm²，差异具有统计学意义(t＝ 6.039，6.593; P<0.05)，在用药不同浓度之间的差异无统计学意义(t＝0.2174，P>0.05)。

口服酪氨酸激酶抑制剂E7080可以抑制激光诱导的大鼠CNV的形成及相关的病理损害。

The aim of this study was to expolre the effect of tyrosine kinase inhibitor E7080 on laser-induced choroidal neovascularization in rats.

Sixty adult male brown Norway rats were provided by Beijing Vital River Laboratory Animal Technology Co. Ltd. They were randomly divided into control group, E7080 low-dose (10 mg·kg^-1·d^-1) group, and E7080 high-dose (20 mg·kg^-1·d^-1) group according to random number table. The choroidal neovascularization was induced by fundus laser photocoagulation. The drug was applied at seven days after laser photocoagulation. Fundus fluorescein angiography was used to check choroidal neovascularization formation and fluorescence leakage at 7 days after laser photocoagulation, 7 days and 14 days after drug administration. The histology of choroidal neovascularization was assessed by histopathological examination at 7 days and 14 days after administration. The area of choroidal neovascularization was observed by staining isolectin B4 on RPE-choroid-sclera flat mounts. The CNV fluorescence signal intensity, thickness and CNV area stained with lectin B4s were statistically described as mean±standard deviation (Mean±SD). The comparison of the mean between different groups among multiple samples adopts repeated measures analysis of variance, and LSD test was used for pairwise comparison.

FFA showed that after 7 days of administration, the relative leakage fluorescence signal intensity of CNV in the low-dose group and the high-dose group were (0.5378±0.0967) and (0.3774±0.086) respectively, which were lower than those of the control group (0.6752±0.095); the difference was statistically significant (t=6.342, 13.99; P<0.05); 14 days after administration, the relative leakage fluorescence signal intensity of CNV in the low-dose group and the high-dose group were (0.5735±0.0726), (0.4071±0.1197), also lower than the control group (0.7305±0.0924); the difference was statistically significant (t=6.92, 14.5; P<0.05). The results of hematoxylin-eosin staining showed that after 7 days of drug treatment, the CNV thickness of the low-dose group and the high-dose group were (84.14±8.829) μm and (77.23±9.365) μm, respectively, which were lower than those of the control group (125.3±18.18) μm; the difference was statistically significant (t=7.38, 8.628; P<0.05); 14 days after drug treatment, the CNV thickness of the low-dose group and the high-dose group were (86.21±10.51) μm and (77.88±7.39) μm, respectively , which were lower than those of the control group (147.9±19.66) μm; the difference is statistically significant (t=9.656, 10.44; P<0.05). Fluorescence staining of the RPE-choroid-sclera flat mounts showed that the average area of choroidal neovascularization in the low-dose group and high-dose group were (18 991±8665) μm² and (20 083±11759) μm², respectively, which were lower than those of the control group (51 156± 24348) μm²; the difference was statistically significant (t= 6.039, 6.593; P<0.05), and there was no significant difference between the low-dose group and high-dose group (t=0.2174, P>0.05).

The tyrosine kinase inhibitor E7080 could inhibit laser-induced choroidal neovascularization and related pathological damage through oral administration in rats.