卡托普利抑制糖尿病视网膜病变大鼠脂代谢紊乱的作用及机制  

Effect and mechanism of captopril on lipid metabolism disorder in diabetic retinopathy rats

作　　者：高翔 刘扣 桂衍超 陈可洋[2] 蒋正轩[1] Gao Xiang;Liu Kou;Gui Yanchao(Dept of Ophthalmology,The Second Affiliated Hospital of Anhui Medical University,Hefei 230601)

机构地区：[1]安徽医科大学第二附属医院眼科,合肥230601 [2]安徽医科大学卫生检验与检疫教研室,合肥230032

出　　处：《安徽医科大学学报》2021年第4期592-595,618,共5页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金青年科学基金(编号:81300755);安徽省青年皖江学者领军骨干人才项目(编号:9101041203)。

摘　　要：目的探讨卡托普利对糖尿病大鼠(DM)脂代谢的影响及与大鼠糖尿病视网膜病变(DR)的关系。方法选取8周龄雄性SD大鼠30只,随机分为正常对照组10只、造模组20只。造模组大鼠采用高脂饲料(HFD)联合链脲佐菌素(STZ)诱导,建立2型糖尿病大鼠(T2DM)模型。将造模组随机分为卡托普利(DM+CAP)组、0.9%氯化钠溶液(DM+NS)组,每组各10只。DM+CAP组大鼠给予卡托普利溶液25 mg/(kg·d)灌胃,DM+NS组给予等体积0.9%氯化钠溶液灌胃,同时每周测定大鼠体质量和空腹血糖。干预8周后将3组大鼠安乐死,收集全血,分离血清,收集视网膜组织。分别检测血清中总胆固醇(TC)、三酰甘油(TG)浓度;观察视网膜组织结构形态,即视网膜内核层、外核层结构变化,新生血管数量;检测大鼠视网膜中胆固醇调节元件结合蛋白质1(SREBP1)、胆固醇调节元件结合蛋白质2(SREBP2)水平。结果卡托普利不能降低大鼠的空腹血糖。与DM+NS组比较,DM+CAP组大鼠血清中TC、TG浓度降低(P<0.01);视网膜组织结构改善:内核层、外核层细胞连接紧密,新生血管数量少;SREBP1、SREBP2表达水平下降(P<0.01)。结论卡托普利可以降低DM血脂相关指标,改善DM视网膜组织形态,降低大鼠视网膜中脂质合成关键酶。其治疗DR的机制可能与其抑制脂质合成的作用有关。Objective To investigate the effect of captopril on lipid metabolism in diabetic mellitus(DM)rats and its relationship with diabetic retinopathy(DR).Methods Thirty male SD rats aged 8 weeks were randomly divided into normal control group(n=10)and model group(n=20).The model rats were induced by high-fat diet(HFD)combined with streptozotocin(STZ)to establish the model of type 2 diabetes mellitus rats.The model rats were randomly divided into captopril group(DM+CAP)and normal saline group(DM+NS)with 10 rats in each group.Rats in DM+CAP group were gavaged with captopril 25 mg/(kg·d),and DM+NS group were gavaged with equal volume normal saline.Body weight and fasting blood glucose were measured weekly.After 8 weeks of intervention,the rats were euthanized,the whole blood was collected,serum was separated and retinal tissue was collected.The concentrations of total cholesterol(TC)and triglyceride(TG)in serum were detected;the structure of retina was observed,including the structure changes of inner and outer nuclear layers,and the number of new blood vessels;the levels of cholesterol regulatory element binding protein 1(SREBP1)and cholesterol regulatory element binding protein 2(SREBP2)were detected.Results Captopril could not reduce fasting blood glucose in rats.Compared with DM+NS group,the concentration of TC and TG in serum of DM+CAP group decreased(P<0.01);the retinal tissue structure improved:the inner and outer nuclear layer cells were tightly connected,the number of new blood vessels was less;the expression levels of SREBP1 and SREBP2 decreased(P<0.01).Conclusion Captopril can reduce the blood lipid related indexes of diabetic rats,improve the retinal tissue morphology,and reduce the key enzymes of lipid synthesis in the retina of diabetic rats.The mechanism may be related to its inhibition of lipid synthesis.

关 键 词：糖尿病视网膜病变 卡托普利 胆固醇 三酰甘油类 胆固醇调节元件结合蛋白质1 胆固醇调节元件结合蛋白2 

分 类 号：R774.1[医药卫生—眼科]