Urantide对动脉粥样硬化大鼠氧化应激及Toll样受体4、髓样分化因子88、核因子κB信号通路表达的影响  

Effects of Urantide on oxidative stress and the expression of toll-like receptor 4/myeloid differentiation factor 88/nuclear transfer factor-κsignaling pathway in atherosclerotic rats

作　　者：刘艳秋[1] 丁兴龙 郭继强 Liu Yanqiu;Ding Xinglong;Guo Jiqiang(Department of Nuclear Medicine,Nanjing Hospital Affiliated to Nanjing Medical University(Nanjing First Hospital),Nanjing 210006,China;Department of Laboratory,General Hospital of Xuzhou Mining Group(the Second Affiliated Hospital of Xuzhou Medical University),Xuzhou 221006,China)

机构地区：[1]南京医科大学附属南京医院(南京市第一医院)核医学科,210006 [2]徐州矿务集团总医院(徐州医科大学第二附属医院),徐州221006

出　　处：《心脑血管病防治》2022年第5期43-47,70,共6页CARDIO-CEREBROVASCULAR DISEASE PREVENTION AND TREATMENT

基　　金：国家重点研发项目:(2019YFF0216501-L33)。

摘　　要：目的探讨Urantide对动脉粥样硬化(AS)大鼠氧化应激及Toll样受体4/髓样分化因子88/核因子κB(TLR4/MyD88/NF-κB)信号通路表达的影响。方法采用腹腔注射维生素D3联合高脂饲料喂养SD大鼠构建AS模型,将成功建模的100只大鼠随机分为模型组、辛伐他汀组、Urantide3 d组、Urantide7 d组、Urantide14 d组,并同时设置正常对照组20只。辛伐他汀组给予辛伐他汀灌胃,连续14 d,Urantide组给予尾静脉注射Urantide,分别连续注射3 d、7 d、14 d,模型组及对照组给予生理盐水灌胃。干预结束后采用HE染色观察各组胸主动脉组织,检测各组血清白介素1β(IL-1β)、白介素6(IL-6)、肿瘤坏死因子α(TNF-α)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、活性氧(ROS)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平以及胸主动脉组织TLR4、MyD88、NF-κB蛋白和mRNA相对表达量。结果HE染色结果显示,模型组出现典型AS病理改变。相较于对照组,模型组、辛伐他汀组、Urantide组TC、TG、LDL-C、MDA、ROS、IL-1β、IL-6、TNF-α水平及TLR4、MyD88、NF-κB蛋白和mRNA相对表达量有所上升(均P<0.05),而HDL-C、SOD、GSH-Px水平有所下降(均P<0.05),且相较于模型组,辛伐他汀组和Urantide组TC、TG、LDL-C、MDA、ROS、IL-1β、IL-6、TNF-α水平及TLR4、MyD88、NF-κB蛋白和mRNA相对表达量更低,而HDL-C、SOD、GSH-Px水平更高(P<0.05),且Urantide组随着干预时间增加,TC、TG、LDL-C、MDA、ROS、IL-1β、IL-6、TNF-α水平及TLR4、MyD88、NF-κB蛋白和mRNA相对表达量更低,而HDL-C、SOD、GSH-Px水平更高(P<0.05)。结论Urantide可显著改善AS大鼠胸主动脉的病理损伤及氧化应激损伤,其可能机制与TLR4/MyD88/NF-κB信号通路有关。Objective To investigate the effect of Urantide on oxidative stress and the expression of toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear transfer factor-κ(NF-κB)signaling pathway in atherosclerotic(AS)rats.Methods Wistar rats were fed with intraperitoneal injection of vitamin D3 and high-fat diet to construct AS model.100 rats successfully modeled were randomly divided into model group,simvastatin group,Urantide 3 d group,Urantide 7 d group,Urantide 14 d group,and set up a normal control group at the same time,20 rats in each group.The simvastatin group was given simvastatin by gavage for 14 days,the Urantide group was given the tail vein injection of Urantide for 3,7,and 14 days respectively,the model group and the control group were given normal saline by gavage.After the intervention,HE staining was used to observe the tissues of the thoracic aorta in each group.The serum levels of interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factorα(TNF-α),and superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),malondialdehyde(MDA),reactive oxygen species(ROS),cholesterol(TC),triglycerides(TG),high density lipoprotein cholesterol(HDL-C),and low density lipoprotein cholesterol(LDL-C)were measured and the relative expression of TLR4,MyD88,NF-κB protein and mRNA in thoracic aorta tissue were detected.Results HE staining showed that the model group had typical AS pathological changes.Compared with the control group,the levels of TC,TG,LDL-C,MDA,ROS,IL-1β,IL-6,TNF-αlevels and TLR4,MyD88,NF-κB protein and mRNA relative expression increased in the model group,simvastatin group and Urantide group,while the levels of HDL-C,SOD,and GSH-Px decreased(P<0.05).Compared with the model group,the levels of TC,TG,LDL-C,MDA,ROS,IL-1β,IL-6,TNF-αand the relative protein and mRNA expression of TLR4,MyD88,NF-κB were lower in the simvastatin group and Urantide group,while the levels of HDL-C,SOD and GSH-Px were higher(P<0.05).In the Urantide groups,the levels of TC,TG,LDL-C,MDA,ROS,IL-1β,IL

关 键 词：URANTIDE 动脉粥样硬化 氧化应激 信号通路 

分 类 号：R543.5[医药卫生—心血管疾病]