环糊精对动脉粥样硬化ApoE^(-/-)小鼠血管功能的影响  

The Effect of Cyclodextrin on Vascular Function in Atherosclerotic ApoE^(-/-)Mice

作　　者：柯永鑫 林立建 KE Yongxin;LIN Lijian(Department of Cardiovascular Medicine,Fuzhou Changle District Hospital,Fuzhou 350005,China)

机构地区：[1]福州市长乐区医院心血管内科,福建福州350005

出　　处：《中国医药指南》2023年第35期48-52,共5页Guide of China Medicine

基　　金：福州市社会发展项目-医疗项目(2021-S-135)。

摘　　要：目的观察环糊精对载脂蛋白E敲除(ApoE^(-/-))小鼠血管功能、血脂及炎症因子的影响,探讨环糊精抑制动脉粥样硬化的可能机制。方法20只8周龄雄性ApoE^(-/-)小鼠被随机分为2组:ApoE^(-/-)+安慰剂(安慰剂组);ApoE^(-/-)+环糊精2 g/kg(环糊精组),每组10只。另外选取10只8周龄正常雄性C57BL/6小鼠作为对照组。对3组每周2次皮下注射给药,连续12周;对照组、安慰剂为等量生理盐水。采用高脂饮食喂养ApoE^(-/-)小鼠构建动脉粥样硬化模型。12周后,对3组小鼠进行下列检测:HE染色观察胸主动脉结构及内膜斑块面积;比色法测血脂水平;血管环试验评估胸主动脉内皮依赖性与非内皮依赖性舒张功能;硫代巴比妥酸(TBA)法测血清丙二醛(MDA)含量;采用酶联免疫吸附测定法(ELISA)测定血清炎症因子(IL-6和NO)水平;采用免疫印迹试验检测小鼠胸主动脉磷酸化p66Shc(p-p66Shc)、核因子κB(NF-κB)p65、内皮型一氧化氮合酶(eNOS)蛋白的水平。结果HE染色显示环糊精显著降低ApoE^(-/-)小鼠胸主动脉内膜斑块面积及血管中膜厚度(P<0.01)。安慰剂组小鼠的血清TG、TC和LDL-C的水平明显高于对照组小鼠(P<0.01)。与对照组相比,安慰剂组胸主动脉对乙酰胆碱介导的内皮依赖性与对硝普钠介导的非内皮依赖性舒张功能降低;与安慰剂组相比,环糊精组胸主动脉内皮依赖性及非内皮依赖性舒张功能均提高(P<0.05)。与对照组相比,安慰剂组小鼠血清MDA、IL-6水平均增加(P<0.01),NO水平均降低(P<0.01);与安慰剂组相比,环糊精组血清MDA、IL-6水平均降低(P<0.01),NO水平均增高(P<0.01)。实验结果表明:相对于对照组,安慰剂组的胸主动脉中p-p66Shc和NF-κB p65蛋白的表达水平增加(P<0.01),eNOS表达水平减少(P<0.01),与安慰剂组相比,ApoE^(-/-)小鼠接受环糊精处理后,胸主动脉中p-p66Shc和NF-κB p65蛋白表达水平下降(P<0.01),eNOS表达水平增高(P<0.01)。结论环糊精�Objective To investigate the effects of cyclodextrin on vascular function,blood lipids,and inflammatory factors in Apolipoprotein E knockout(ApoE^(-/-))mice.Methods Twenty 8-week-old male ApoE^(-/-)mice were assigned randomly to two groups:ApoE^(-/-)+placebo group,and ApoE^(-/-)+cyclodextrin group(2 g/kg),with 10 mice in each group.A high-fat diet was given to induce atherosclerosis in ApoE^(-/-)mice.Cyclodextrin was administered subcutaneously twice a week for 12 weeks.C57BL/6 mice(n=10)were used as the control group.HE staining was employed to examine the morphology of the thoracic aorta and quantify the area of endometrial plaques.Blood lipid levels were measured by colorimetry.Myography was used to assess the diastolic response of the thoracic aorta to acetylcholine and sodium nitroprusside.Malondialdehyde content was measured by thiobarbituric acid.Serum levels of inflammatory factors(IL-6,and NO)were measured by ELISA.Western blot test was performed to detect the levels of phosphorylated p66Shc,NF-κB p65,and eNOS protein in the thoracic aorta.Results Cyclodextrin was found to significantly reduce plaque area and vascular membrane thickness in the thoracic aorta of ApoE^(-/-)mice(P<0.01).Mice in the ApoE^(-/-)group had significantly higher levels of serum triglycerides,total cholesterol,and LDL-C compared to the control group(P<0.01).Vasodilation in response to ACTH and SNP was reduced in the ApoE^(-/-)group compared to the control group.However,vasodilation was significantly improved in the ApoE^(-/-)+cyclodextrin group(P<0.05).The ApoE^(-/-)group exhibited increased serum levels of MDA,IL-6,as well as decreased NO levels compared to the control group(P<0.01).In contrast,the ApoE^(-/-)+cyclodextrin group showed reduced levels of MDA,IL-6,and increased NO level(P<0.01).Western blot analysis revealed increased expression levels of p-p66Shc and NF-κB p65 protein,and decreased expression levels of eNOS in the thoracic aorta of the ApoE^(-/-)group compared to the control group(P<0.01).However,the ApoE^(-/-)+cy

关 键 词：环糊精 ApoE^(-/-) 动脉粥样硬化 氧化应激 炎症 内皮功能 

分 类 号：R972.6[医药卫生—药品]