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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

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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-KB信号通路有关。
Effects of Eriocitrin on oxidative stress and inflammatory response in carotid atherosclerosis rats by reg-ulating Nrf2/NQO-1/HO-1/NF-κB signaling pathway
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 factor κB(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-1 β,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-Nrf2/Nrf2,NQO-1,HO-1 levels were obviously increased(P<0.05);Brusatol reversed the improve-ment effect of Eriocitrin on oxida-tive stress and inflammatory response in CAS rats(P<0.05).Conclusion Erioc-itrin can regulate the level of blood lipids,as well as inhibit inflammatory response and oxidative stress in CAS rats,and its mechanism of action may be related to the regulation of Nrf2/NQO-1/HO-1/NF-κB signaling pathway.

Carotid artery diseasesEriocitrinOxidative stressInflammationSignal transduction

潘建立、郑良英、方杰、叶成杰

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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

浙江大学药物安全评价研究中心GLP实验室,浙江杭州 310000

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

颈动脉疾病 圣草次苷 氧化应激 炎症 信号传导

2024

中国药物与临床
中国医院协会

中国药物与临床

影响因子:0.846
ISSN:1671-2560
年,卷(期):2024.24(15)