环缩酚肽抑制小鼠血管增殖性视网膜病变的研究

Cyclic Heptadepsipeptide Inhibited Retinal Neovascularization and Nonperfusion in Oxygen Induced Ischemic Retinopathy Mice

【目的】观察两种环缩酚肽的衍生物(Hep-A)和(Hep-B)对氧诱导的血管增殖性视网膜病变的抑制作用。【方法】将鼠龄为7d(P7)的C57BL/6幼鼠置于体积分数75%的氧气箱中连续生活5d,建立氧诱导的血管增殖性视网膜病变模型。在12d(P12)幼鼠回到正常大气环境中,同时开始给小鼠皮下注安慰剂(第1组,n=23)、Hep-A10mg/kg(第2组,n=22)、或者Hep-B10mg/kg(第3组,n=22),每天两次,持续5d。在17d(P17)取鼠眼进行冰冻切片和GSA(griffoniasimplicifolialectinB4)染色,或作荧光素灌注和视网膜平铺片,用图象分析软件定量计算视网膜无灌注区和新生血管的面积。【结果】病理检测视网膜新生血管面积:第一组为(0.51±0.08)mm2/鼠(n=7);第2组为(0.11±0.01)mm2/鼠(n=8);第3组为(0.16±0.02)mm2/鼠(n=8)。视网膜平片检测视网膜新生血管面积:第1组为(1.36土0.02)mm2/眼(n=32),第2组为(0.19±0.01)mm2/眼(n=28),第3组为(0.07±0.01)mm2/眼(n=28);视网膜平片检测视网膜无灌注区面积:第1组为(2.33±0.08)mm2/眼,第2组为(1.08±0.09)mm2/眼,第3组为(1.22±0.11)mm2/眼。经ANOVA分析,第2组和第3组分别与第1组比较,视网膜新生血管的面积和视网膜无灌注区的面积,均明显减少,差异有统计学意义(P<0.01)。【结论】两种环缩酚肽衍生物均能强效?

To investigate the effects of two novel fungus derived cyclic heptadepsipeptide (Hep A) and (Hep B) on oxygen induced ischemic retinopathy in mice.The C57BL/6 mice were placed in 75%oxygen from postnatal day (P) 5 to P12. At P12, the mice were put back in room air and treated with subcutaneous injection of 10 mg/kg Hep A, 10 mg/kg Hep B, or vehicle twice a day. At P17, mice were either sacrificed and eye frozen sections were stained with griffonia simplicifolia lectin B4 (GSA) which selectively stained vascular cells and counterstained with eosin; or perfused with fluorescein dextran and then made retinal flat mount. The areas of the retinal neovascularization or retinal nonperfusion were tested under microscopy and recorded by a vadio camera and frame grabber, and then quantitated by Image Pro Plus sofeware. The data were analyzed by ANOVA software.Compared to vehicle treated mice, the area of retinal nonperfusion and neovascularization in oxygen induced ischemic retinopathy mice treated with Hep A or Hep B was significantly reduced.[Conclusion]The analogs of cyclic heptadepsipeptide potently inhibit retinal nonperfusion and neovascularization in oxygen induced ischemic retinopathy mice.