圣草次苷调节Nrf2/NQO-1/HO-1/NF-κB信号通路对颈动脉粥样硬化的影响  

Effects of Eriocitrin on oxidative stress and inflammatory response in carotid atherosclerosis rats by regulating Nrf2/NQO-1/HO-1/NF-κB signaling pathway

作　　者：潘建立 郑良英 方杰[2] 叶成杰 Pan Jianli;Zheng Liangying;Fang Jie;Ye Chengjie(Department of Pharmacy,Hangzhou Campus,Wenzhou Medical University Affiliated Eye and Vision Hospital,Hangzhou,Zhejiang 310020,China;GLP Laboratory,Drug Safety Evaluation Research Center,Zhejiang Univer-sity,Hangzhou,Zhejiang,310020,Cnina;Department of Pharmacy,Yuying Children′s Hospital,Second Affiliat-ed Hospital of Wenzhou Medical University,Wenzhou,Zhejiang 325000,China)

机构地区：[1]温州医科大学附属眼视光医院杭州院区药剂科,浙江杭州310020 [2]浙江大学药物安全评价研究中心GLP实验室,浙江杭州310000 [3]温州医科大学附属第二医院育英儿童医院药剂科,浙江温州325000

出　　处：《中国药物与临床》2024年第15期968-973,I0001,I0002,共8页Chinese Remedies & Clinics

摘　　要：目的探究圣草次苷对颈动脉粥样硬化(CAS)大鼠氧化应激和炎症反应的影响,并探讨其作用机制。方法将大鼠随机分为对照组、模型组、圣草次苷低剂量组、圣草次苷中剂量组、圣草次苷高剂量组、圣草次苷高剂量+Brusatol组,每组10只。构建CAS大鼠模型,检测各组大鼠血脂指标三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C),苏木精-伊红(HE)染色观察颈动脉组织病理变化,油红O染色观察颈动脉组织脂质堆积情况,试剂盒检测氧化应激指标丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT),酶联免疫吸附试验检测活性氧(ROS)及炎性细胞因子白细胞介素(IL)-1β、IL-10、肿瘤坏死因子-α(TNF-α)水平,蛋白质免疫印迹法检测核因子E2相关因子2(Nrf2)/醌氧化还原酶1(NQO1)/血红素加氧酶1(HO-1)/核转录因子κB(NF-κB)信号通路蛋白表达。结果与对照组相比,模型组大鼠颈动脉组织内膜增厚,动脉粥样硬化斑块和脂质沉积增加,TG、TC、LDL-C、脂质堆积比例、IL-1β、TNF-α、MDA、ROS、p-NF-κB、p65/NF-κB p65水平上升,HDL-C、IL-10、SOD、CAT、p-Nrf2/Nrf2、NQO-1、HO-1下降(P<0.05);与模型组相比,圣草次苷低、中、高剂量组颈动脉组织内膜相对完整,动脉粥样硬化斑块和脂质沉积减少,TG、TC、LDL-C、脂质堆积比例、IL-1β、TNF-α、MDA、ROS、p-NF-κB p65/NF-κB p65水平下降,HDL-C、IL-10、SOD、CAT、p-Nrf2/Nrf2、NQO-1、HO-1上升(P<0.05);Brusatol逆转圣草次苷对CAS大鼠氧化应激和炎症反应的改善(P<0.05)。结论圣草次苷能调节CAS大鼠的血脂水平,抑制炎症反应和氧化应激,其作用机制可能与调节Nrf2/NQO-1/HO-1/NF-κB信号通路有关。Objective To explore the effects of Eriocitrin on oxidative stress and inflammatory response in carotid atherosclerosis(CAS)rats,and to explore its mechanism.Methods Rats were randomly divided into a control group,a model group,a low-dose Eriocitrin group,a medium-dose Eriocitrin group,a high-dose Eriocitrin group,and a high-dose Eriocitrin+Brusatol group,with 10 rats in each group.CAS rat model was constructed,and blood lipid indicators such as triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C)were detected,hematoxylin-eosin(HE)staining was applied to observe pathological changes in carotid artery tissue,oil red O staining was applied to observe the lipid accumula-tion in carotid tissue,kits were applied to detect oxidative stress indicators such as malondialdehyde(MDA),su-peroxide dismutase(SOD),and catalase(CAT),enzyme-linked immunosorbent assay kit was applied to detect lev-els of reactive oxygen species(ROS)and inflammatory cytokines such as interleukin-1β(IL-1β),IL-10,and tumor necrosis factor-α(TNF-α),and Western blot was applied to detect the expression of nuclear factor E2 related fac-tor 2(Nrf2)/quinone oxidoreductase 1(NQO1)/heme oxygenase 1(HO-1)/nuclear factorκB(NF-κB)signaling path-way proteins.Results Compared with the control group,the carotid artery tissue intima of rats in the model group was obviously thickened,the AS plaques and lipid deposition were increased,the TG,TC,LDL-C,proportion of lipid accumulation,IL-1β,TNF-α,MDA,ROS,p-NF-κB p65/NF-κB p65 levels were obviously increased,and the HDL-C,IL-10,SOD,CAT,p-Nrf2/Nrf2,NQO-1,HO-1 levels were obviously decreased(P<0.05);compared with the model group,the carotid artery tissue intima of the low,medium,and high dose Eriocitrin groups was relatively intact,the AS plaques and lipid deposition was decreased,the TG,TC,LDL-C,proportion of lipid accumulation,IL-1β,TNF-α,MDA,ROS,p-NF-κB p65/NF-κB p65 levels were obviously decreased,and the HDL-C,IL-10,SOD,CAT,p-

关 键 词：颈动脉疾病 圣草次苷 氧化应激 炎症 信号传导 

分 类 号：R285.5[医药卫生—中药学]