替米沙坦对糖尿病动脉粥样硬化大鼠视黄醇结合蛋白4的作用

目的 研究视黄醇结合蛋白4(RBP4)与晚期氧化蛋白产物(AOPP)在糖尿病动脉粥样硬化大鼠血清中的表达及替米沙坦的干预作用.方法 45只SPF级健康Wistar雄性大鼠按随机数字表法分为正常对照组(A组)和糖尿病动脉粥样硬化组(B组)及药物干预组(C组),每组15只.A组饲普通饲料.B、C组大鼠饲以高脂高糖饲料并予腹腔一次性大剂量注射链脲佐菌素及予维生素D3灌胃,建立糖尿病动脉粥样硬化模型.8周证实造模成功后,B组为糖尿病动脉粥样硬化组,继续饲高脂高糖饲料,C组为药物干预组,饲高脂高糖饲料同时予替米沙坦5 mg·kg~(-1)·d~(-1)灌胃.实验共16周,实验结束后所有大鼠空腹隔夜,10%水合氯醛腹腔麻醉后心脏采血离心分离血清测血脂、RBP4及AOPP含量.处死大鼠取腹主动脉做HE染色.结果 B、C组大鼠血脂、RBP4、AOPP水平与A组比较差异有统计学意义(P均＜0.05).相关分析结果显示RBP4与AOPP呈正相关(r=0.505,P＜0.05).多元逐步回归显示AOPP是糖尿病大血管病变的主要危险因素,RBP4、甘油三酯是AOPP的主要危险因素.腹主动脉HE染色显示B组大鼠动脉壁内侧内膜有纤维组织增生,部分纤维化和玻璃样变,并见明显钙化.C组大鼠动脉壁内侧内膜仅有轻微纤维化及玻璃样变.结论 RBP4可能通过影响血脂分布及增强血管内膜氧化应激参与糖尿病大血管病变的发生发展,替米沙坦对糖尿病大血管病变有保护作用.

Expression of retinol-binding protein 4 in rats with diabetes and atherosclerosis and the intervention of telmisartan

Objective To assay serum retinal binding protein 4(RBP4)and advanced oxidation protein product(AOPP)levels in rats with diabetes and atherosclerosis,and to explore the correlation between RBP4 and Diabetic macroangiopathy.Methods 45 healthy male Wistar rats in SPF level were randomly divided into 3 groups(n=15).Group A for the normal group,fed normal diet.Group B for diabetic atherosclerosis group.Group C for diabetes atherosclerosis intervention group plus telmisartan.Rats in group B and C were fed with high fat and high sugar diet,and to a one-time high-dose intraperitoneal injection of streptozotocin(STZ)and to vitamin D3 orally,make the establishment of diabetic atherosclerosis model.Two mouths later,modeling success was confirmed,rats in group B were continued feeding high-fat and high-sugar diet,C group fed high-fat and high-sugar diet as well as simultaneously to telmisartan (5 mg·kg~(-1)·d~(-1)gavage.Experiment lasted 16 weeks,all rats after fasting overnight,10% chloral hydrate intraperitoneal anesthesia,centrifugal separation after the cardiac blood serum,automatic biochemical analyzer measured serum TC,TG,HDL-C,LDL-C.Enzyme-linked immunosorbent assay (ELISA)measured serum RBP4,UV speetrophotometer measured serum AOPP content.Execution of the rat abdominal aorta to do HE staining.Results Surem TG,TC,LDL-C in group B increased than those in group A,and surem HDL-C reduced.But it is not obvious that surem TG,TC,LDL-C in group C increased and HDL-C were lower than group A.RBP4 and AOPP in group B were significantly higher,but group C significantly reduced after the intervention of telmisartan.RBP4 correlated with AOPP.Abdominal aortic HE staining showed in group B fibrous tissue of the artery intimal medial wall were hyperplasia,and some fibrosis and hyalinization,and calcification significantly.In group C artery intimal medial wall showed only slight fibrosis and hyalinization.Conclusions Based on the above results,we speculate that RBP4 may affect the blood lipid profile and intima enhanced oxidative stress involved in diabetic macroangiopathy of the occurrence and development.