腺病毒介导Profurin表达改善ApoE－/－小鼠斑块稳定性

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腺病毒介导Profurin表达改善ApoE－/－小鼠斑块稳定性
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                        张心怡1,2,3张心怡
山东第一医科大学山东省医学科学院附属省立医院急诊科,山东省济南市 250021;山东第一医科大学山东省医学科学院实验动物学院山东省实验动物中心,山东省济南市 250117;山东第一医科大学山东省医学科学院临床与基础医学院,山东省济南市 250117
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王晨1,2王晨
山东第一医科大学山东省医学科学院附属省立医院急诊科,山东省济南市 250021;山东第一医科大学山东省医学科学院实验动物学院山东省实验动物中心,山东省济南市 250117
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杨婉越1,2,3杨婉越
山东第一医科大学山东省医学科学院附属省立医院急诊科,山东省济南市 250021;山东第一医科大学山东省医学科学院实验动物学院山东省实验动物中心,山东省济南市 250117;山东第一医科大学山东省医学科学院临床与基础医学院,山东省济南市 250117
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杨泽1,2,3,4杨泽
山东第一医科大学山东省医学科学院附属省立医院急诊科,山东省济南市 250021;山东第一医科大学山东省医学科学院实验动物学院山东省实验动物中心,山东省济南市 250117;山东第一医科大学山东省医学科学院临床与基础医学院,山东省济南市 250117;山东第一医科大学山东省医学科学院第二附属医院,山东省泰安市 271000
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任国栋1,2任国栋
山东第一医科大学山东省医学科学院附属省立医院急诊科,山东省济南市 250021;山东第一医科大学山东省医学科学院实验动物学院山东省实验动物中心,山东省济南市 250117
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张继国5张继国
山东第一医科大学山东省医学科学院药学院,山东省济南市 250117
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于杨1,2,3于杨
山东第一医科大学山东省医学科学院附属省立医院急诊科,山东省济南市 250021;山东第一医科大学山东省医学科学院实验动物学院山东省实验动物中心,山东省济南市 250117;山东第一医科大学山东省医学科学院临床与基础医学院,山东省济南市 250117
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张科1,2,3张科
山东第一医科大学山东省医学科学院附属省立医院急诊科,山东省济南市 250021;山东第一医科大学山东省医学科学院实验动物学院山东省实验动物中心,山东省济南市 250117;山东第一医科大学山东省医学科学院临床与基础医学院,山东省济南市 250117
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作者单位:(1.山东第一医科大学(山东省医学科学院)附属省立医院急诊科,山东省济南市 250021;2.山东第一医科大学(山东省医学科学院)实验动物学院(山东省实验动物中心),山东省济南市 250117;3.山东第一医科大学(山东省医学科学院)临床与基础医学院,山东省济南市 250117;4.山东第一医科大学(山东省医学科学院)第二附属医院,山东省泰安市 271000;5.山东第一医科大学(山东省医学科学院)药学院,山东省济南市 250117)
作者简介:张心怡,硕士研究生,研究方向为脂质代谢与动脉粥样硬化,E-mail:xinyizhang202209@163.com。王晨,硕士研究生,研究方向为脂质代谢与动脉粥样硬化,E-mail:2544230241@qq.com。张心怡与王晨为共同第一作者。通信作者于杨,博士,教授,硕士研究生导师,研究方向为脂质代谢与动脉粥样硬化和炎症性疾病,E-mail:yyu@sdfmu.edu.cn。通信作者张科,博士,副主任医师,研究方向为脂质代谢与动脉粥样硬化,E-mail:zhangxiaotian1029@163.com。
通讯作者:
基金项目:国家自然科学基金面上项目(81970385)；山东省自然基金面上项目(ZR2019MH021、ZR2022MH202和ZR2023MH361)；泰安市科技创新发展项目(2023NS379)

Adenovirus mediated Profurin expression improved the plaque stability of ApoE－/－ mice

Author:

ZHANG Xinyi ^{^1,2,3}
ZHANG Xinyi
Emergency Department of Shandong Provincial Hospital Affiliated to Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250021, China;School of Laboratory Animal Shandong Laboratory Animal Center, Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China;School of Clinical and Basic Medical Sciences, Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China
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WANG Chen ^{^1,2}
WANG Chen
Emergency Department of Shandong Provincial Hospital Affiliated to Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250021, China;School of Laboratory Animal Shandong Laboratory Animal Center, Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China
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YANG Wanyue ^{^1,2,3}
YANG Wanyue
Emergency Department of Shandong Provincial Hospital Affiliated to Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250021, China;School of Laboratory Animal Shandong Laboratory Animal Center, Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China;School of Clinical and Basic Medical Sciences, Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China
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YANG Ze ^{^1,2,3,4}
YANG Ze
Emergency Department of Shandong Provincial Hospital Affiliated to Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250021, China;School of Laboratory Animal Shandong Laboratory Animal Center, Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China;School of Clinical and Basic Medical Sciences, Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China;The Second Affiliated Hospital of Shandong First Medical University Shandong Academy of Medical Sciences, Taian, Shandong 271000, China
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REN Guodong ^{^1,2}
REN Guodong
Emergency Department of Shandong Provincial Hospital Affiliated to Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250021, China;School of Laboratory Animal Shandong Laboratory Animal Center, Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China
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ZHANG Jiguo ^⁵
ZHANG Jiguo
School of Pharmacy, Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China
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YU Yang ^{^1,2,3}
YU Yang
Emergency Department of Shandong Provincial Hospital Affiliated to Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250021, China;School of Laboratory Animal Shandong Laboratory Animal Center, Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China;School of Clinical and Basic Medical Sciences, Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China
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ZHANG Ke ^{^1,2,3}
ZHANG Ke
Emergency Department of Shandong Provincial Hospital Affiliated to Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250021, China;School of Laboratory Animal Shandong Laboratory Animal Center, Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China;School of Clinical and Basic Medical Sciences, Shandong First Medical University Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China
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Affiliation:

1.Emergency Department of Shandong Provincial Hospital Affiliated to Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, Shandong 250021, China;2.School of Laboratory Animal (Shandong Laboratory Animal Center), Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, Shandong 250117, China;3.School of Clinical and Basic Medical Sciences, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, Shandong 250117, China;4.The Second Affiliated Hospital of Shandong First Medical University (Shandong Academy of Medical Sciences), Taian, Shandong 271000, China;5.School of Pharmacy, Shandong First Medical University (Shandong Academy of Medical Sciences), Jinan, Shandong 250117, China)

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摘要:

目的]探究腺病毒介导Profurin(PF)表达对ApoE－/－小鼠斑块稳定性的影响。 [方法]用高脂饲料喂养ApoE－/－小鼠8周,给予腺病毒(ADV)介导的PF干预,继续高脂饲料喂养4周,分离主动脉根部,进行动脉粥样硬化斑块面积分析和免疫组织化学分析。用荧光供体法检测血浆磷脂转运蛋白(PLTP)活性,用酶学试剂盒检测血浆总胆固醇(TC)、甘油三酯(TG),用快速蛋白液相色谱进行脂蛋白谱分析。 [结果]与对照组相比,ADV-PF组小鼠血浆TC和TG水平、PLTP活性以及循环中肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)水平均显著下降(P＜0.01)；ADV-PF组小鼠全长主动脉内表面动脉粥样硬化病变无明显变化,但主动脉根部斑块面积和斑块内脂质面积均缩小(P＜0.01),巨噬细胞含量显著降低(P＜0.01),平滑肌细胞和胶原面积无明显差别；斑块内基质金属蛋白酶9含量显著降低(P＜0.05)。 [结论]过表达PF能在一定程度上减轻动脉粥样硬化并降低循环炎症因子水平,有效改善ApoE－/－小鼠斑块稳定性。

关键词:动脉粥样硬化;斑块稳定性;脂蛋白;磷脂转运蛋白;Profurin

Abstract:

Aim To investigate the effect of adenovirus (ADV)-mediated Profurin (PF) expression on the plaque stability of ApoE－/－ mice. Methods ApoE－/－ mice were fed with high-fat diet for 8 weeks, and then treated with ADV-mediated PF intervention, followed by high-fat diet for 4 weeks. Aortic roots were isolated for atherosclerotic plaque area analysis and immunohistochemical analysis. Plasma phospholipid transfer protein (PLTP) activity was detected by fluorescence donor essay, plasma total cholesterol (TC) and triglyceride (TG) were measured by enzyme assay kits, and fast protein liquid chromatography was used for lipoprotein profile analysis. Results Compared with the control group, the plasma TC and TG levels, PLTP activity and circulating tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels in ADV-PF group were significantly decreased (P＜0.01). In the ADV-PF group, there was no significant change in atherosclerotic lesions on the inner surface of the full-length aorta, but the plaque area and lipid area in the aortic root were reduced (P＜0.01), the content of macrophages was significantly decreased (P＜0.01), and the smooth muscle cells and collagen area were not significantly different. The content of matrix metalloproteinase-9 in plaque was significantly decreased (P＜0.05). Conclusion Overexpression of PF can alleviate atherosclerosis and reduce the levels of circulating inflammatory factors to a certain extent, and effectively improve the plaque stability of ApoE－/－ mice.

Key words:atherosclerosis; plaque stability; lipoprotein; phospholipid transfer protein; Profurin

参考文献

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张心怡,王晨,杨婉越,杨泽,任国栋,张继国,于杨,张科.腺病毒介导Profurin表达改善ApoE－/－小鼠斑块稳定性[J].中国动脉硬化杂志,2025,33(4):297~302.

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收稿日期:2024-12-16
最后修改日期:2025-02-28
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在线发布日期: 2025-05-16

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