VEGF、SDF-1在糖尿病视网膜血管病变发生、发展中的作用及机制

The mechanism of VEGF and SDF-1 in the development of diabetic retinal vascular lesions

目的探讨血管内皮生长因子(vascular endothelial growth factor,VEGF)、基质细胞衍生因子(stromal cell derived factor-1,SDF-1)在糖尿病视网膜血管病变中的作用机制。方法运用链脲佐菌素(STZ)注射及脂肪乳灌胃的方法构建糖尿病大鼠模型、糖尿病合并视网膜病变大鼠模型。随机分为对照组、糖尿病组、糖尿病合并视网膜病变12 w组、糖尿病合并视网膜病变24 w组,每组30只。对各组制模大鼠给予玻璃体内注射贝伐单抗进行干预,4 w后,处死动物提取视网膜组织。观察干预前后大鼠视网膜组织病理学变化,检测视网膜组织中VEGF、SDF-1基因和蛋白的表达。结果干预前,糖尿病组大鼠视网膜镜下表现与对照组大致相似,血管未见明显异常;糖尿病合并视网膜病变12 w组大鼠视网膜镜下可见各层细胞排列不整齐,偶见毛细血管内皮细胞突出内界膜;糖尿病合并视网膜病变24 w组大鼠视网膜镜下可见视网膜内界膜水肿明显,各层细胞排列明显不整齐,较多血管内皮细胞突出内界膜。干预后,对照组和糖尿病组大鼠视网膜组织镜下表现与干预前均无明显差异;糖尿病合并视网膜病变12 w组和糖尿病合并视网膜病变24 w组大鼠视网膜镜下均可见视网膜内界膜水肿明显减轻,毛细血管内皮细胞突出内界膜的情况明显得到改善。干预前,对照组、糖尿病组、糖尿病合并视网膜病变12 w组和糖尿病合并视网膜病变24 w组大鼠的视网膜组织中VEGF、SDF-1蛋白和基因的表达逐渐升高,4组间比较差异有统计学意义(F=8.56、7.46,P<0.05)。干预后4组大鼠的视网膜组织中VEGF、SDF-1蛋白和基因的表达均出现下降,以糖尿病合并视网膜病变12 w组和糖尿病合并视网膜病变24 w组下降更明显,4组间比较差异有统计学意义(F=9.06,7.26、P<0.05)。结论 VEGF、SDF-1参与了糖尿病视网膜血管病变的发生,阻断VEGF的表达能明显改善视网膜血管病变,且抑制VEGF表达可以下调SDF-1表达水平。

Objective To measure mechanism of VEGF and SDF-1 in the development of diabetic retinal vascular lesions. Methods The gastric diabetic rats model and the rat model with diabetic retinopathy were constructed by the chain urea with cephalosporins（ streptozocin,STZ） and fat emulsion injected. Rats were randomly divided into control group,diabetes group,diabetic retinopathy 12 w,diabetic retinopathy 24 wgroup,and 30 rats in each group. All rats were injected with bevacizumab to intervene. After 4 weeks,the rats were killed and the retinal tis-sue were extracted. The pathology change of retinal tissue before and after intervention were observed the expression of VEGF and SDF-1 gene and protein in retinal tissue of rats were detected. Results Before intervention,the pathology change of control group and diabetes group were similar,there were no obvious abnormal vessels. In diabetic retinopathy 12 weeks group,each layer cells in the rat retina were irregular arrangement and a little capillary endothelial cells were out of the occasional border membrane. In diabetic retinopathy 24 weeks group,boundary membrane were obviously edema and irregular arrangement of each layer cell membrane was more,and more capillary endothelial cells were prominent out of the border membrane. After the intervention,there were no obvious difference in the pathology change between control group and diabetes group. In diabetic retinopathy 12 weeks group and diabetic retinopathy rat retina microscopically 24 weeks group,the edema in the retina boundary membranewere obviously lightened,the capillary endothelial cells out of the boundary membrane were significantly reduced. Before the intervention,the expression of VEGF and SDF-1 protein and gene in the control group,diabetes group,diabetic retinopathy 12 weeks group and diabetic retinopathy 24 weeks group were increased in sequence,and there were significant differences（ F = 8. 56,7. 46,P〈0 05）. After the intervention,the expression of VEGF and SDF-1protein and gene in the retinal tissue of four groups,the control group,diabetes group,diabetic retinopathy 12 weeks group and diabetic retinopathy 24 weeks group,were decreased gradually,especially in diabetic retinopathy12 weeks group and diabetic retinopathy 24 weeks group,and there were significant differences（ F = 9. 06,7. 26,P〈0 05）. Conclusion VEGF,SDF-1 was involved in the occurrence of diabetic retinal vascular lesions. Blocking the expression of VEGF can obviously improve the retinal vascular lesions,and inhibiting the expression of VEGF expression can cut the expression of SDF-1.