目的：建立链脲佐菌素(streptozotocin， STZ)诱导的小鼠增殖性糖尿病视网膜病(proliferative diabetic retinopathy， PDR)动物模型，并观察在增殖性糖尿病视网膜病发生、发展过程中血管内皮生长因子(vascular endothelial growth factor， VEGF)及其受体(VEGFR1， VEGFR2)，金属基质蛋白酶(matrix metalloproteinase， MMP)2， MMP9表达的变化。

方法：C57BL/6J小鼠连续5d腹腔注射STZ(55 mg/kg)。末次注射后7d检测血糖浓度。糖尿病诱导成功的小鼠和正常小鼠继续饲养3～5mo。实验结束后进行视网膜病理组织观察，并利用CD31免疫荧光染色检测视网膜血管的分布情况。采用实时定量荧光PCR分析检测VEGF， VEGFR1， VEGFR2， MMP2， MMP9的基因表达。

结果：视网膜组织病理观察和CD31免疫荧光染色实验结果均表明5月龄的糖尿病小鼠视网膜组织中血管数目明显比同月龄正常小鼠多。同时，与同月龄正常小鼠相比，5月龄糖尿病小鼠视网膜组织中VEGF， VEGFR1， VEGFR2， MMP2， MMP9的基因表达也明显增加。

结论：本研究表明STZ诱导的糖尿病小鼠在5月龄时发生了增殖性糖尿病视网膜病的病变，期间视网膜组织中VEGF， VEGFR1， VEGFR2， MMP2， MMP9的基因表达都明显增加。

AIM: To establish the mice model of streptozotocin(STZ)-induced proliferative diabetic retinopathy(PDR), and observe the altered expression of some pro-angiogenic molecules such as vascular endothelial growth factor(VEGF)and its receptors(VEGFR1 and VEGFR2), and matrix metalloproteinase(MMP2 and MMP9)during the development of PDR.

METHODS:C57BL/6J mice were intraperitoneal injected with STZ(55 mg/kg)for 5 consecutive days, and blood glucose concentrations were measured after 7d of the injection. The diabetic mice were further housed for 3, 4, 5mo respectively after the development of diabetes. Histological evaluation of retinas was performed. The retinal vessels were detected by immunofluorescence staining with the cluster of differentiation 31(CD31). The mRNA expression of VEGF, VEGFR1, VEGFR2, MMP2 and MMP9 in mice retinas was detected by Real-time PCR analysis.

RESULTS: Retinal histological observation and CD31 staining both demonstrate that there are more vessels in diabetic mice than in normal control mice at 5mo after the development of diabetes. As compared with normal control, the mRNA expression of VEGF, VEGFR1, VEGFR2, MMP2 and MMP9 are all increased in diabetic mice at 5mo after the development of diabetes.

CONCLUSION: This study demonstrates that PDR is occurred at 5mo after the development of diabetes in STZ-induced diabetic mice. In addition, the mRNA expression of VEGF, VEGFR1, VEGFR2, MMP2 and MMP9 are all increased after the development of PDR.

国家自然科学基金(No.81173517)