大鼠类糖尿病性视网膜病变模型的构建及对比研究

Establishment and contrast aoalysis of rat models of diabetes-like retinopathy

目的观察和比较不同血清蛋白来源的外源性非酶糖基化终末产物(AGEs)构建大鼠类糖尿病性视网膜病变模型的异同。方法分别利用鼠血清蛋白(RSA)和牛血清蛋白(BSA)体外孵育AGEs。28只SD大鼠随机分为AGE-BSA组、AGE-RSA组、BSA对照组和RSA对照组(n=7)。AGE-BSA组和AGE-RSA组大鼠,自尾静脉注射40 mg/kg体外孵育的相应AGEs,1次/d,连续2周。利用视网膜消化铺片技术结合HE染色和AGEs单克隆抗体免疫组化观察视网膜毛细血管内改变。结果2周后两AGE组大鼠视网膜毛细血管内出现AGEs沉积;AGE-BSA组大鼠视网膜血管出现周细胞丢失,而AGE-RSA组未出现此改变;各组内皮细胞均未发生改变。结论使用外源性AGEs能够模拟类似的糖尿病大鼠视网膜早期病变,并且建模时间短;与RSA比较,BSA结合的AGEs可能更易模拟类糖尿病视网膜早期病变。

Objective To investigate similarities and differences between animal models of diabetes-like retinopathy induced with exogenous advanced glycation end products （AGEs） derived from different albumin. Methods Exogenous AGEs were prepared with rat serum albumin （RSA） or bovine serum albumin （ BSA）. Twenty-eight SD rats were randomly divided into AGE-BSA group, AGE-RSA group, BSA control group and RSA control group （n = 7）. Rats in AGE-BSA group and AGE-RSA group were injected with corresponding AGEs at 40 mg· kg^-1 ·d^-1 through tail vein for two weeks. Retinal vascular preparation technique with HE staining or with immunochemistry using anti-AGEs monoclonal antibody was adopted to detect the changes in retinal capillaries. Results Exogenous AGEs deposited in retinal capillaries in AGE groups in two weeks. Pericyte loss in retinal capillaries was observed in AGE-BSA group, but not in AGE-RSA group. No changes were found in endothelial cells in each group. Conclusion Exogenous AGEs can be used to establish early diabetic retinopathy model in rats in a short duration. AGEs with BSA may be more suitable to simulate early diabetes-like retinopathy than AGEs with RSA.