VEGF抑制剂对糖尿病性视网膜病变模型大鼠的干预效果及对CRA血流动力学的影响

Intervention effect of VEGF inhibitor on diabetic retinopathy model rats and its influence on CRA hemodynamics

目的研究血管内皮生长因子(vascular endothelial growth factor,VEGF)抑制剂对糖尿病性视网膜病变模型大鼠的干预效果及对视网膜中央动脉(central retinal artery,CRA)血流动力学的影响。方法 40只SPF级、健康雄性大鼠,随机选取10只为对照组,建模成功30只大鼠随机分为模型组(生理盐水)、无菌柠檬酸组(无菌柠檬酸)、VEGF抑制剂组(贝伐单抗)各10只。测定CRA血流舒张期最低流速(EDV)、收缩期峰值血流速度(PSV)、阻力指数(RI)、搏动指数(PI)及Ras、Raf-1及ERK表达。结果与模型组相比,无菌柠檬酸组、VEGF抑制剂组EDV(31.53±8.42/47.46±10.29/90.26±16.55 mm/s,F/P=14.956/0.001)、PSV(58.92±11.37/84.16±14.52/155.57±18.67 mm/s,F/P=21.116/0.001)、脂联素水平升高;RI(1.12±0.32/0.85±0.20/0.68±0.18,F/P=7.046/0.001)、PI(1.35±0.35/0.91±0.22/0.69±0.12,F/P=8.861/0.001)、血液流变学指标、空腹血糖、VEGF、ICAM-1、IL-1β水平,Ras、Raf-1及ERK表达量降低,差异具有统计学意义(P<0.05)。与无菌柠檬酸组相比,VEGF抑制剂组EDV(47.46±10.29/90.26±16.55 mm/s,t/P=6.945/0.001)、PSV(84.16±14.52/155.57±18.67 mm/s,t/P=9.548/0.001)、脂联素水平升高;RI(0.85±0.20/0.68±0.10,t/P=2.404/0.027)、PI(0.91±0.22/0.69±0.12,t/P=2.776/0.012)、血液流变学指标、空腹血糖、VEGF、ICAM-1、IL-1β水平,Ras、Raf-1及ERK表达量降低,差异具有统计学意义(P<0.05)。结论 VEGF抑制剂可改善糖尿病性视网膜病变模型大鼠CRA血流动力学与血液流变学指标,降低VEGF、ICAM-1及IL-1β水平,抑制血管新生。

Objective To study the intervention effect of vascular endothelial growth factor( VEGF) inhibitors on diabetic retinopathy model rats and the hemodynamics of central retinal artery( CRA). Methods Of 40 specific-pathogenfree healthy male rats,10 were randomly selected as the control group. The remaining 30 rats were successfully modeled and randomly divided into the model group( normal saline),sterile citric acid group( sterile citric acid) and VEGF inhibitor group( bevacizumab)( n = 10). The minimum diastolic velocity( EDV) of the CRA was measured. Results Compared with the model group,the levels of EDV( 31. 53 ± 8. 42/47. 46 ± 10. 29/90. 26 ± 16. 55 mm/s,F/P = 14. 956/0. 001),peak systolic velocity( PSV;58. 92 ± 11. 37/84. 16 ± 14. 52/155. 57 ± 18. 67 mm/s,F/P = 21. 116/0. 001) and adiponectin were increased in the aseptic citric acid and VEGF inhibitor groups. In addition,the resistivity index( RI;1. 12±0. 32/0. 85±0. 20/0. 68±0. 18,F/P = 7. 046/0. 001),pulsatility index( PI;1. 35±0. 35/0. 91±0. 22/0. 69±0. 12,F/P = 8. 861/0. 001),hemorheological indicators,fasting blood glucose,VEGF,intercellular adhesion molecule 1( ICAM-1),interleukin-1( IL-1) and expression levels of Ras,Raf and extracellular signal-regulated kinase( ERK) were significantly decreased( P<0. 05). Compared with the aseptic citric acid group,the levels of EDV( 47. 46±10. 29/90. 26±16. 55 mm/s,T/P = 6. 945/0. 001),PSV( 84. 16± 14. 52/155. 57± 18. 67 mm/s,T/P = 9. 548/0. 001) and adiponectin were increased in the VEGF inhibitor group. Furthermore,the RI( 0. 85 ± 0. 20/0. 68 ± 0. 10,T/P = 2. 404/0. 027),PI( 0. 91±0. 22/0. 69±0. 12,T/P = 2. 776/0. 012),hemorheological indicators,fasting blood glucose,VEGF,ICAM-1,IL-1 and expression of Ras,Raf-1,and ERK were significantly decreased( P< 0. 05). Conclusions VEGF inhibitors can improve the CRA hemodynamics and hemorheology indices of diabetic retinopathy model rats,reduce the levels of VEGF,ICAM-1 and IL-1β and inhibit angiogenesis.