目的:探讨坎地沙坦(candesartan,Can)对大鼠糖尿病视网膜病变(diabetic retinopathy,DR)的作用机制。方法:雄性SD大鼠45只,取8只作为正常对照组,其余大鼠尾静脉注射链脲佐菌素(STZ)建立糖尿病模型,剔除死亡及未成模大鼠5只,将成模大鼠随机分为4组:糖尿病组、Can治疗组、胰岛素治疗组、Can与胰岛素联合治疗组,每组8只。饲养12wk,放射免疫法检测血浆血管紧张素Ⅱ(AngⅡ)含量,免疫组织化学方法检测AngⅡ1型受体(AT1R)、核因子-κB(NF-κB)在视网膜组织中的蛋白表达。结果:各组血浆AngⅡ浓度均增高,胰岛素组较糖尿病组明显降低,Can组较糖尿病组显著增高;正常对照组视网膜均有少量AT1R和NF-κB蛋白表达,糖尿病组表达显著增高,各治疗组均可使其表达下降,以Can与胰岛素联合治疗组下降最显著。结论:Can通过抑制视网膜AngⅡ和AT1R结合,减少AT1R和NF-κB的激活,以治疗DR。

AIM:To investigate the effect and mechanism of candesartan(Can) for diabetic retinopathy(DR) in rats.METHODS:Of 45 male SD rats,8 rats were obtained at random as normal control group.The diabetic rat model was built by tail vein injection of streptozotocin(STZ).Except for 5 died or not successful model rats,successful model rats were randomly divided into diabetes group,Can treatment group,insulin treatment group,Can and insulin treatment group.Per group had 8 rats.The plasma AngⅡ was determined by radioimmunoassay,and retinal AT1R,NF-κB protein expressions were measured by immunohistochemistry.RESULTS:The plasma AngⅡ increased in all groups.Compared with diabetes group,insulin treatment group decreased significantly,and Can treatment group increased significantly.Normal control group had little AT1R,NF-κB protein expression.The expression of AT1R,NF-κB protein levels increased significantly in diabetes group.It all decreased in these treatment groups,and it decreased significantly in Can and insulin treatment groups.CONCLUSION:Can can inhibit the combination of Ang Ⅱ and AT1R,and it decreases the expression of AT1R,NF-κB protein levels.Therefore,candesartan has protective effect on DR.

中国辽宁省科技攻关计划资助项目(No.2009225010-45)