Celik Fatih, Ulaş Fatih, Ozünal Zeynep Güneş, Fırat Tülin, Celebi Serdal, Doğan Umit
Department of Ophthalmology, Faculty of Medicine, Abant Izzet Baysal University, Bolu 14280, Turkey.
Department of Medical Pharmacology, Faculty of Medicine, Abant Izzet Baysal University, Bolu 14280, Turkey.
Int J Ophthalmol. 2014 Feb 18;7(1):57-61. doi: 10.3980/j.issn.2222-3959.2014.01.10. eCollection 2014.
To evaluate the influence of an intravitreal injection of bevacizumab and fasudil on the retinal vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNFα), and caspase 3 levels in a diabetic rabbit model.
The study included 6 healthy rabbits (Group 1), 6 rabbits with experimentally induced diabetes mellitus (DM) (Group 2), 7 rabbits with experimentally induced DM to which intravitreal bevacizumab was administered (Group 3), and 7 rabbits with experimentally induced DM to which intravitreal fasudil was administered (Group 4). An intravitreal injection of 1.25mg/50µL bevacizumab in the right eye of rabbits in Group 3 and an intravitreal injection of 0.0064mg/50µL fasudil in the right eye of rabbits in Group 4 were administered on day 21 after the induction of DM. The studied eyes of the rabbits were enucleated three days after the intravitreal injection. The TNFα, VEGF, and caspase 3 levels were determined using the ELISA method.
There was a statistically significant difference in the VEGF and caspase 3 levels between groups (P=0.005 and P =0.013, respectively), but the TNFα level did not differ significantly between groups (P=0.792). It was found that VEGF levels were significantly lower in Group 1 and Group 3 than in Group 2 using the Mann-Whitney U test with the Bonferroni correction (P=0.004 for both comparison). There was no statistically significant difference between other groups with regard to VEGF levels (the P value ranged between 0.015 and 0.886). Although the P values of the caspase 3 levels were 0.015 for Group 1 and Group 4, 0.038 for Group 2 and Group 3, and 0.018 for Group 3 and Group 4, these P values remained above the threshold P value of 0.0083, which was the statistically significant level for post hoc tests.
An intravitreal injection of bevacizumab decreased both the VEGF level, which plays a role in angiogenesis, and the caspase 3 level, which plays a role in apoptosis. Although not as effective as bevacizumab, fasudil had a beneficial effect on the VEGF levels but significantly increased the caspase 3 levels.
评估玻璃体内注射贝伐单抗和法舒地尔对糖尿病兔模型视网膜血管内皮生长因子（VEGF）、肿瘤坏死因子α（TNFα）和半胱天冬酶3水平的影响。
本研究纳入6只健康兔（第1组）、6只实验性诱导糖尿病（DM）兔（第2组）、7只实验性诱导DM且玻璃体内注射贝伐单抗的兔（第3组）和7只实验性诱导DM且玻璃体内注射法舒地尔的兔（第4组）。在诱导DM后第21天，对第3组兔右眼玻璃体内注射1.25mg/50µL贝伐单抗，对第4组兔右眼玻璃体内注射0.0064mg/50µL法舒地尔。玻璃体内注射3天后摘除兔的研究眼。采用酶联免疫吸附测定（ELISA）法测定TNFα、VEGF和半胱天冬酶3水平。
各组间VEGF和半胱天冬酶3水平存在统计学显著差异（分别为P = 0.005和P = 0.013），但TNFα水平在各组间无显著差异（P = 0.792）。采用经Bonferroni校正的Mann-Whitney U检验发现，第1组和第3组的VEGF水平显著低于第2组（两组比较P均为0.004）。其他组间VEGF水平无统计学显著差异（P值介于0.015和0.886之间）。虽然第1组和第4组半胱天冬酶3水平的P值为0.015，第2组和第3组为0.038，第3组和第4组为0.018，但这些P值仍高于事后检验的统计学显著水平阈值P值0.0083。
玻璃体内注射贝伐单抗可降低在血管生成中起作用的VEGF水平以及在细胞凋亡中起作用的半胱天冬酶3水平。法舒地尔虽不如贝伐单抗有效，但对VEGF水平有有益作用，但显著升高了半胱天冬酶3水平。
