血竭乙酸乙酯提取物改善ApoE^(-/-)小鼠动脉粥样硬化的药效与作用机制研究  

Effect and mechanism of EtOAc extract of Draconis Sanguis on improving atherosclerosis in ApoE^(-/-)mice

作　　者：赵一慕 王鑫玉 裴钰洁 薛伟刚 王俊娇 逄雪萍 王凌潇 赵云芳[1] 霍会霞 屠鹏飞[3] 郑姣[1] 李军[1,2] ZHAO Yi-mu;WANG Xin-yu;PEI Yu-jie;XUE Wei-gang;WANG Jun-jiao;PANG Xue-ping;WANG Ling-xiao;ZHAO Yun-fang;HUO Hui-xia;TU Peng-fei;ZHENG Jiao;LI Jun(Modern Research Center for Traditional Chinese Medicine,Beijing Research Institute of Chinese Medicine,Beijing University of Chinese Medicine,Beijing 102488,China;School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China;State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Science,Peking University,Beijing 100191,China)

机构地区：[1]北京中医药大学中医药研究院中药现代研究中心,北京102488 [2]北京中医药大学中药学院,北京102488 [3]北京大学药学院天然药物与仿生药物国家重点实验室,北京100191

出　　处：《中国中药杂志》2024年第11期2973-2980,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(82030114,82074050);北京市自然科学基金项目(7232296)。

摘　　要：探讨血竭乙酸乙酯提取物(EtOAc extract of Draconis Sanguis,DSE)改善ApoE基因敲除小鼠(ApoE^(-/-))动脉粥样硬化的体内药效及作用机制。ApoE^(-/-)小鼠随机分为对照组,模型组,依折麦布阳性药(5 mg·kg^(-1))组和DSE低(100 mg·kg^(-1))、高(200 mg·kg^(-1))剂量组,灌胃给药,持续16周,在给药期间除对照组外,各组小鼠均给予高脂饲料喂饲。给药16周后测量小鼠体质量、肝脏及附睾脂肪质量,检测血脂水平、主动脉流出道斑块面积等指标的差异,评估DSE的体内药效。体外培养人脐静脉内皮细胞(HUVEC),利用氧化低密度脂蛋白(ox-LDL)诱发内皮细胞氧化应激,检测DSE对内皮细胞氧化应激相关蛋白的影响。结果表明,低、高剂量的DSE均改善了动脉粥样硬化ApoE^(-/-)小鼠的附睾脂肪质量和附睾脂肪指数,降低血浆总胆固醇、甘油三酯、非高密度脂蛋白胆固醇水平,减少主动脉流出道斑块面积。体外实验证实,ox-LDL显著增加HUVEC中脂质过氧化标志物4-羟基壬烯醛(4-HNE)的水平,确认DSE通过抑制ox-LDL诱发的血管内皮细胞氧化应激,改善ApoE^(-/-)小鼠的动脉粥样硬化病变程度。This study aims to investigate the effect and mechanism of the EtOAc extract of Draconis Sanguis(DSE)on improving atherosclerosis in ApoE gene knockout(ApoE^(-/-))mice.The ApoE^(-/-)mice were randomly divided into five groups:control group,model group,positive group treated with ezetimibe of 5 mg·kg^(-1)(EG),and low(100 mg·kg^(-1))and high dose(200 mg·kg^(-1))groups of DSE.Except for the control group,all other groups were fed a high-fat diet and administered drugs for 16 successive weeks.After 16 weeks of administration,the body weight,liver,and epididymal fat mass of the mice were measured;the level of blood lipid and the plaque area of the aortic outflow tract were detected to evaluate the efficacy of DSE in vivo.In addition,in vitro cultures of human umbilical vein endothelial cell(HUVEC)were conducted.Oxidative stress of endothelial cells was induced by oxidized low-density lipoprotein(ox-LDL),and the effects of DSE on oxidative stress-related proteins in endothelial cells were examined.The results showed that both doses of DSE significantly improved the epididymal fat mass and index of ApoE^(-/-)mice with atherosclerosis,lowered the levels of plasma total cholesterol,triglyceride,and non-high density lipoprotein cholesterol,and reduced the plaque area of the aortic outflow tract.In vitro experiments confirmed that ox-LDL significantly increased the level of lipid peroxidation marker 4-HNE in HUVEC cells,confirming that DSE improved the degree of atherosclerotic lesions in ApoE^(-/-)mice by inhibiting ox-LDL-induced oxidative stress in vascular endothelial cells.

关 键 词：血竭乙酸乙酯提取物 动脉粥样硬化 氧化应激 脂质过氧化 

分 类 号：R285.5[医药卫生—中药学]