人参皂苷Rg3对糖尿病视网膜病变大鼠PI3K-Akt/PKB通路和血管内皮生长因子、细胞间黏附分子-1表达的影响  

Effects of ginsenoside Rg3 on PI3K-Akt/PKB pathway and expression levels of vascular endothelial growth factor and intercellular adhesion molecule-1 in rats with diabetic retinopathy

作　　者：王皎皎 胡燃燃 张丹 谯雁彬 WANG Jiaojiao;HU Ranran;ZHANG Dan;QIAO Yanbin(Department of Ophthalmology,Chongqing Armed Police Corps Hospital,Chongqing 400061,China;Department of Ophthalmology,Chongqing General Hospital,Chongqing 400013,China)

机构地区：[1]武警重庆总队医院眼科,重庆市400061 [2]重庆市人民医院眼科,重庆市400013

出　　处：《眼科新进展》2020年第1期20-25,共6页Recent Advances in Ophthalmology

基　　金：重庆市卫生计划委员会医学科研项目(编号:2015HBRC-011)

摘　　要：目的研究人参皂苷Rg3对糖尿病视网膜病变大鼠PI3K-Akt/PKB通路和血管内皮生长因子(vascular endothelial growth factor,VEGF)、细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)表达的影响。方法将60只SD大鼠随机分为对照组、模型组、人参皂苷Rg3治疗高剂量组(H-Rg3组,5.0 mg·kg^-1 Rg3)、低剂量组(L-Rg3组,0.5 mg·kg^-1 Rg3),每组各15只,构建糖尿病视网膜病变大鼠模型,共治疗28 d。检测各组大鼠视网膜组织中丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)和乳酸脱氢酶(lactate dehydrogenase,LDH)表达;HE染色和TUNEL染色分析病理变化;免疫组织化学检查ICAM-1和VEGF蛋白的表达;Western blot检测视网膜组织中PI3K、Akt、p-Akt蛋白的表达;采用LY294002抑制剂(静脉注射,0.5 mg·kg^-1)验证PI3K-Akt/PKB通路。结果与对照组相比,模型组凋亡细胞比例、视网膜组织中MDA和LDH表达均升高(均为P<0.05),SOD、PI3K和p-Akt蛋白表达均降低(均为P<0.05),VEGF、ICAM-1、Bad、cleaved-Caspase-3蛋白表达均升高(均为P<0.05)。与模型组相比,L-Rg3组和H-Rg3组凋亡细胞比例、视网膜组织中MDA和LDH表达均降低(均为P<0.05),SOD、PI3K和p-Akt蛋白表达均升高(均为P<0.05),VEGF、ICAM-1、Bad、cleaved-Caspase-3蛋白表达均降低(均为P<0.05)。与L-Rg3组相比,H-Rg3组凋亡细胞比例、视网膜组织中MDA和LDH表达均降低(均为P<0.05),SOD、PI3K和p-Akt蛋白表达均升高(均为P<0.05),VEGF、ICAM-1、Bad、cleaved-Caspase-3蛋白表达均降低(均为P<0.05)。与LY-模型组相比,LY294002组VEGF、ICAM-1、Bad和cleaved-Caspase-3蛋白表达均升高(均为P<0.05),Bcl-2蛋白表达降低(P<0.05)。与LY-Rg3组相比,LY-Rg3+LY294002组VEGF、ICAM-1、Bad和cleaved-Caspase-3蛋白表达均升高(均为P<0.05),Bcl-2蛋白表达降低(P<0.05)。结论人参皂苷Rg3能够通过激活PI3K-Akt/PKB信号通路,下调VEGF和ICAM-1蛋白的表达,保护糖尿病视网膜病变大鼠的视网膜组织。Objective To investigate the effects of ginsenoside Rg3 on PI3K-Akt/PKB pathway and expression levels of vascular endothelial growth factor(VEGF)and intercellular adhesion molecule-1(ICAM-1)in rats with diabetic retinopathy.Methods A total of 60 SD rats were randomly divided into control group,model group,high-dose ginsenoside Rg3(H-Rg3;5.0 mg·kg^-1 Rg3)treatment group and low-dose Rg3(L-Rg3;0.5 mg·kg^-1 Rg3)treatment group,15 rats in each group.The rats treated for 28 days to construct models of diabetic retinopathy.The levels of malondialdehyde(MDA),superoxide dismutase(SOD)and lactate dehydrogenase(LDH)in retinal tissues were detected.HE staining and TUNEL staining were performed for pathological analysis.Immunohistochemistry method was used to analyze the expression levels of VEGF and ICAM-1.Western blot was used to analyze the expression levels of PI3k,Akt and p-AKT.The PI3K-Akt/PKB pathway was validated by the LY294002 inhibitor(intravenous injection,0.5 mg·kg^-1).Results Compared with control group,the proportion of apoptotic cells,levels of MDA and LDH in retinal tissues increased(all P<0.05),while levels of SOD,PI3K and p-Akt decreased(all P<0.05),and levels of VEGF,ICAM-1,Bad,cleaved-Caspase-3 increased(all P<0.05)in model group.Compared with the model group,the proportion of apoptotic cells,levels of MDA and LDH in retinal tissues significantly decreased(all P<0.05),while levels of SOD,PI3K and p-Akt obviously increased(all P<0.05),and the expression levels of VEGF and ICAM-1 in retinal tissues were significantly inhibited(all P<0.05)in L-Rg3 group and H-Rg3 group.Compared with L-Rg3 group,the proportion of apoptotic cells,levels of MDA and LDH in retinal tissues significantly decreased(all P<0.05),while the levels of SOD,PI3K and p-Akt obviously increased(all P<0.05),and the expression levels of VEGF and ICAM-1 in retinal tissues were significantly inhibited(all P<0.05)in H-Rg3 group.Compared with LY-model group,expression levels of VEGF,ICAM-1,Bad and cleaved-Caspase-3 obviously increased and Bcl-

关 键 词：人参皂苷RG3 糖尿病视网膜病变 PI3K-Akt/PKB通路 血管内皮生长因子 细胞间黏附分子-1 

分 类 号：R774.1[医药卫生—眼科]