替米沙坦对糖尿病小鼠早期视网膜病变的抑制作用及机制  

Inhibitory effects and mechanism of Telmisartan on early diabetic retinopathy in STZ-induced diabetes mice

作　　者：曹子群 姜涛[1] 宗瑶 杨雪娇 王云霄[1] 孙哲[1] 葛朋飞 CAO Zi-Qun;JIANG Tao;ZONG Yao;YANG Xue-Jiao;WANG Yun-Xiao;SUN Zhe;GE Peng-Fei(From the Department of Ophthalmology,the Affiliated Hospital of Qingdao University,Qingdao 266000,Shandong Province,China)

机构地区：[1]青岛大学附属医院眼科,山东省青岛市266000

出　　处：《眼科新进展》2019年第5期419-423,427,共6页Recent Advances in Ophthalmology

基　　金：山东省自然科学基金资助(编号:ZR2018BH013)~~

摘　　要：目的探讨玻璃体内注射替米沙坦对小鼠糖尿病视网膜病变(diabetic retinopathy,DR)的影响及其保护机制。方法取健康成年雄性C57BL/6J小鼠70只,将小鼠随机分成空白对照组(10只)、溶剂对照组(10只)和糖尿病组(50只);采用腹腔注射链脲佐菌素(streptozotocin,STZ)建立糖尿病小鼠模型,溶剂对照组腹腔注射等剂量的柠檬酸钠缓冲液,依据造模后左眼玻璃体内所给予药物将糖尿病组小鼠随机分为替米沙坦组、康柏西普组和模型对照组。采用Western-blotting检测各组小鼠视网膜中血管内皮生长因子A (vascular endothelial growth factor-A,A VEGF-A)、晚期糖基化终末产物受体(receptor for advanced glycosylation end product,RAGE)、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)蛋白的表达,通过HE染色在光学显微镜下观察各组小鼠视网膜形态学的变化,利用荧光血管造影观察各组小鼠视网膜血流灌注的状态。结果 Western-blotting结果显示:模型对照组与空白对照组相比,VEGF-A、RAGE、TNF-α的蛋白表达均明显升高(均为P<0.001);替米沙坦组左眼较右眼VEGF-A、RAGE、TNF-α的蛋白表达均明显降低(均为P<0.001);康柏西普组左眼较右眼VEGF-A、RAGE、TNF-α的蛋白表达均降低(均为P<0.01);溶剂对照组与空白对照组相比,VEGF-A、RAGE、TNF-α的蛋白表达差异均无统计学意义(均为P>0.05),模型对照组左眼与右眼相比VEGF-A、RAGE、TNF-α的蛋白表达差异均无统计学意义(均为P>0.05)。HE染色显示,空白对照组小鼠视网膜各层细胞分界清晰,形态正常,神经细胞排列整齐;模型对照组小鼠视网膜各层分界不清,细胞发生空泡样变,神经细胞排列不整齐;替米沙坦组小鼠左眼较右眼视网膜损伤程度减轻;康柏西普组小鼠左眼较右眼视网膜损伤程度减轻。荧光血管造影显示:空白对照组视网膜血流灌注均匀充盈;模型对照组视网膜血流灌注不均匀,血管形态迂曲;替米沙坦Objective To investigate the protective effect of telmisartan on diabetic retinopathy (DR) by intravitreous injection in mice. Methods Seventy healthy adult male C57BL/6J mice were randomly divided into three groups:blank control group ( n =10),solvent control group ( n =10) and diabetic group ( n =50).The diabetic mice model was established by injection of streptozotocin intraperitoneally (streptozotocin,STZ).The solvent control group was injected with same dosage of sodium citrate buffer (vehicle) intraperitoneally.Based on the medicine injected into the left eyes after modeling,the diabetic mice were divided into telmisartan group,compastep group,and the model control group.Western-blotting was used to detect the protein expression levels of vascular endothelial growth factor A (VEGF-A),receptor for advanced glycation end product (RAGE) and tumor necrosis factor-alpha (TNF-α) in the retina of mice.Morphological changes in retina in each group were observed under a light microscope by HE staining.The retinal blood perfusion status of each group was observed by fluorescence reperfusion angiography. Results Western-blotting showed that the protein expression levels of VEGF-A,RAGE and TNF-α was significantly increased in the model control group compared with the blank control group (all P <0.001).In Telmisartan group,the expression levels of VEGF-A,RAGE and TNF-α in the left eyes were significantly lower than that in the right eyes (all P <0.001).In Compastep group,the expression levels of VEGF-A,RAGE and TNF-α in the left eyes were lower than that in the right eyes (all P <0.01).Compared with the blank control group,there was no significant difference in the protein expression of VEGF-A,RAGE and TNF-α between the solvent control group and the blank control group (all P >0.05);There was no significant difference in the protein expression of VEGF-A,RAGE and TNF-α between the left eyes and the right eyes of the model control group (all P >0.05).HE staining showed that the cells in each layer of retina from the

关 键 词：糖尿病视网膜病变 替米沙坦 血管内皮生长因子A 晚期糖基化终末产物 肿瘤坏死因子α 

分 类 号：R774.1[医药卫生—眼科]