摘要
目的:内皮抑制素是一种内源性血管内皮细胞的强效抑制剂,实验拟验证局部应用重组内皮抑制素滴眼液对大鼠角膜移植术后新生血管的抑制作用。方法:实验于2005-09/2006-03在重庆医科大学附属第一医院实验动物中心完成。①选用清洁级成年雌性SD大鼠(受体)60只,Wistar大鼠(供体)30只,建立大鼠同种异体穿透性角膜移植模型,供体提供双眼角膜,受体均选择右眼手术。移植术后按随机数字表法分成内皮抑制素组和对照组,分别用50mg/L的内皮抑制素眼液及赋形剂滴眼。②于术后1周、2周、3周、1个月及2个月5个时间点,麻醉后每组随机处死6只大鼠。观察角膜新生血管生长状况;比较各组角膜植片透明度、水肿、新生血管程度及移植排斥反应指数;检测角膜植片上内皮抑制素及血管内皮生长因子的表达情况。结果:60只受体大鼠全部进入结果分析。①内皮抑制素组大鼠角膜新生血管面积显著低于对照组(P<0.05￣0.01)。②内皮抑制素组大鼠的排斥反应指数在术后1周、2周、3周、1个月及2个月均低于对照组(P<0.05￣0.01)。③与对照组相比,内皮抑制素组角膜植片组织中内皮抑制素的表达明显增强(P<0.05￣0.01),血管内皮生长因子的表达明显降低(P<0.05￣0.01)。结论:内皮抑制素滴眼液可以有效抑制大鼠角膜移植术后角膜新生血管的形成,下调角膜植片中血管内皮生长因子的表达,从而降低角膜移植术后免疫排斥反应的发生,为临床防治角膜移植术后新生血管提供了新的思路。
AIM: Endostatin (ES) is one kind of powerful inhibitors of endogenous vascular endothelial cells. This study evaluates the effects of ES eyedrops on inhibiting the corneal neovascularization by topical instillation on the rat model of penetrating keratoplasty (PKP). METHODS: The experiment was carried out in the Test Animal Center of the First Affiliated Hospital, Chongqing Medical University from September 2005 to March 2006.①PKP was performed orthotopically from 30 Wistar rats to 60 SD recipient adult female rats of cleaning grade. All recipient rats in right eyes were randomly assigned to experimental group and control group after PKP. The experimental group was treated with 50 mg/L ES eyedrops, while the control group was treated with excipient eyedrops.②Every 6 animals in two groups were killed respectively after anesthesia in the 1st week, 2nd week, 3rd week, 1st month and 2nd month postoperatively. The corneal opacity, edema and corneal neovascularization were recorded and compared, and then the rejection index was calculated. ES and vascular endothelial growth factor (VEGF) expression was also examined. RESULTS: All the 60 recipient rats were involved in the result analysis.①The experimental group showed significantly smaller areas of new blood vessels than control group (P < 0.05-0.01).②The rejection index of the experimental group was lower obviously than the control group at five time points (P < 0.05-0.01).③Compared with the control group, significantly increased ES expression was observed in the experimental group (P < 0.05-0.01). VEGF expression was significantly decreased in the experimental group (P < 0.05-0.01). CONCLUSION: Topical application of ES eyedrops can prevent the corneal neovascularization of corneal allografts, reduce VEGF expression in corneal allografts and then suppress effectively the postoperative corneal allograft rejection, which will provide a new therapy for corneal neovascularization in clinic.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2007年第51期10221-10225,共5页
Journal of Clinical Rehabilitative Tissue Engineering Research
