黄芪甲苷Ⅳ对2型糖尿病大鼠视网膜的保护作用  

Protective Effect of Astragaloside Ⅳ on the Retina of Type 2 Diabetic Rats

作　　者：李昌[1] 王爱玲 赵增强[1] 张占海 张琮 张丽 LI Chang;WANG Ailing;ZHAO Zengqiang;ZHANG Zhanhai;ZHANG Cong;ZHANG Li(Department of Traditional Chinese Medicine,Nanyang Medical College,Nanyang 473000;Department of Critical Care Medicine,Nanyang Central Hospital,Nanyang 473000;Department of Cardiology,First Affiliated Hospital of Nanyang Medical College,Nanyang 473000)

机构地区：[1]南阳医学高等专科学校中医系,南阳473000 [2]南阳市中心医院重症医学科,南阳473000 [3]南阳医专第一附属医院心内科,南阳473000

出　　处：《中药药理与临床》2024年第5期63-67,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：河南省医学科技攻关计划(编号:20190902)。

摘　　要：目的:本研究旨在探讨黄芪甲苷Ⅳ对高脂肪饮食和链脲佐菌素(STZ)诱导的糖尿病(DM)大鼠视网膜病变(DR)的作用。方法:雄性Wistar大鼠分为:正常对照组、模型对照组、黄芪甲苷Ⅳ0.02、0.04、0.08 g/kg组和羟苯磺酸钙0.5 g/kg组。高脂肪饮食和STZ诱导DR大鼠模型,各组大鼠灌胃相应药物或生理盐水,1次/d,连续12 w。称体质量,测定空腹血糖(FBG)和血糖化血红蛋白(HbA1c)含量;眼底照相造影估算视网膜血管直径;伊文思蓝染料外渗技术测定视网膜血管通透性;测定视网膜白细胞数目;试剂盒检测视网膜中抗氧化标志物和促炎细胞因子水平;Western blot法检测血管细胞黏附分子1(VCAM-1)、低氧诱导因子-1α(HIF-1α)和血管内皮生长因子A(VEGF-A)蛋白的表达。结果:与正常对照组比较,模型对照组大鼠体质量明显降低,血糖、糖化血红蛋白含量明显升高(P<0.05),出现血管渗漏并伴有血管扩张,大鼠视网膜渗漏增加,白细胞面积明显增加(P<0.05),视网膜中SOD、CAT和GSH活力或含量明显降低(P<0.05),TNF-α、IL-1β和IL-6含量明显升高(P<0.05),VCAM-1、HIF-1α和VEGF-A蛋白表达明显上调(P<0.05);与模型对照组比较,黄芪甲苷IV 0.04、0.08 g/kg组大鼠体质量明显增加,血糖含量和糖化血红蛋白含量明显降低(P<0.05),大鼠视网膜小动脉和小静脉轻度扩张,视网膜渗漏和白细胞面积明显减少(P<0.05),视网膜中SOD、CAT和GSH活力或含量明显升高(P<0.05),TNF-α、IL-1β、IL-6含量和VCAM-1、HIF-1α、VEGF-A蛋白表达明显降低(P<0.05)。结论:黄芪甲苷IV对DR的保护作用可能与抗炎、抗氧化、下调HIF-1α/VEGF-A信号通路有关。Objective:To investigate the effect of astragaloside Ⅳ(AS-Ⅳ)on high-fat diet and streptozotocin(STZ)-induced diabetic retinopathy(DR)in rats.Methods:Male Wistar rats were divided into normal control group,model control group,AS-Ⅳ 0.02,0.04 and 0.08 g/kg groups,and calcium dobesilate(CaD)0.5 g/kg group.High-fat diet and STZ were used to induce DR rat model.Rats in all groups were given corresponding drugs or normal saline,once per day for 12 consecutive weeks.The body weight,fasting blood glucose(FBG)and glycosylated hemoglobin(HbA1c)were measured.Fundus photography was performed to estimate retinal vascular diameter.Evans blue(EB)dye extravasation was used to detect retinal vascular permeability.Retinal leukocyte count was determined.The levels of antioxidant markers and pro-inflammatory cytokines were determined by kits,and the protein expressions of vascular cell adhesion molecule 1(VCAM-1),hypoxia-inducible factor-1α(HIF-1α)and vascular endothelial growth factor A(VEGF-A)were detected by Western blot.Results:Compared with the conditions in normal control group,the body weight was decreased in model control group,the contents of FBG and HbA1c were increased(P<0.05),vascular leakage and hemangiectasis were observed,the retinal vascular permeability and leukocyte deposition were enhanced(P<0.05),the contents or activities of SOD,CAT and GSH were lowered(P<0.05),while the contents of inflammatory factors TNF-α,IL-1βand IL-6 as well as the protein expressions of VCAM-1,HIF-1αand VEGF-A were elevated(P<0.05).Compared with the model control group,the AS-Ⅳ 0.04 and 0.08 g/kg groups had gained body weight,reduced FBG and HbA1c(P<0.05),expanded retinal vascular diameter of arteriole and venule,decreased retinal vascular permeability and leukocyte deposition(P<0.05),up-regulated SOD,CAT and GSH(P<0.05),while down-regulated TNF-α,IL-1β,IL-6,VCAM-1,HIF-1αand VEGF-A(P<0.05).Conclusion:The protective effect of AS-Ⅳ on DR may be related to the anti-inflammatory and antioxidant functions,as well as the down-r

关 键 词：黄芪甲苷Ⅳ 糖尿病视网膜病变 糖化血红蛋白 炎症 血管细胞黏附分子1 

分 类 号：R285.5[医药卫生—中药学]