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黄芪甲苷Ⅳ对2型糖尿病大鼠视网膜的保护作用

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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Ⅳ 0.02、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.
Protective Effect of Astragaloside Ⅳ on the Retina of Type 2 Diabetic Rats
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 giv-en corresponding drugs or normal saline,once per day for 12 consecutive weeks.The body weight,fasting blood glucose(FBG)and glycosy-lated 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-in-ducible 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-1α and 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 diame-ter 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-1α and VEGF-A(P<0.05).Conclusion:The protective effect of AS-Ⅳon DR may be related to the anti-inflammatory and antioxidant functions,as well as the down-regulation of HIF-1α/VEGF-A signaling path-way.

Astragaloside ⅣDiabetic retinopathy(DR)Glycosylated hemoglobin(HbA1c)InflammationVascular cell adhesion mole-cule 1(VCAM-1)

李昌、王爱玲、赵增强、张占海、张琮、张丽

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南阳医学高等专科学校中医系,南阳 473000

南阳市中心医院重症医学科,南阳 473000

南阳医专第一附属医院心内科,南阳 473000

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

河南省医学科技攻关计划

20190902

2024

中药药理与临床
中国药理学会 四川省中医药科学院

中药药理与临床

北大核心
影响因子:0.996
ISSN:1001-859X
年,卷(期):2024.40(5)
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