上海交通大学学报（医学版）

›› 2012, Vol. 32 ›› Issue (8): 1056-.doi: 10.3969/j.issn.1674-8115.2012.08.020

• 论著（基础研究） • 上一篇    下一篇

SUMO特异性蛋白酶1在动脉粥样硬化发病机制中的作用

黄 弦1, 吴 际1, 程金科2   

  1. 1.上海交通大学 生命科学技术学院生物化学与分子生物学系, 上海 200240； 2.上海交通大学 基础医学院生物化学与分子细胞生物学系, 上海 200025
  • 出版日期:2012-08-28 发布日期:2012-08-29
  • 通讯作者: 程金科, 电子信箱: jkcheng@shsmu.edu.cn。
  • 作者简介:黄 弦（1987—）, 男, 硕士生；电子信箱: g11510910@gmail.com。

Role of SUMO-specific protease 1 in pathogenesis of atherosclerosis

HUANG Xian1, WU Ji1, CHENG Jin-ke2   

  1. 1.Department of Biochemistry and Molecular Biology, School of Life Sciences and Biotechnology, Shanghai Jiaotong University, Shanghai 200240, China；2.Department of Biochemistry and Molecular Cellular Biology, Basic Medical College, Shanghai Jiaotong University, Shanghai 200025, China
  • Online:2012-08-28 Published:2012-08-29

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摘要：

目的 探讨SUMO特异性蛋白酶1（SENP1）在小鼠动脉粥样硬化发病机制中的作用。方法 采用主动脉整体和主动脉根部油红O染色以及主动脉根部巨噬细胞标志物MOMA-2的免疫组织化学染色，观察SENP1+/+ X Apoe－/－（n=5）与SENP1+/－ X Apoe－/－（n=4）两组小鼠在饲喂高胆固醇高脂食物后动脉粥样硬化病理改变。采用乙酰化低密度脂蛋白（ac-LDL）诱导巨噬细胞RAW264.7泡沫化，油红O染色检测RAW264.7 si-ns及RAW264.7 si-SENP1的泡沫细胞形成能力。采用Real-Time PCR和Western blotting分别检测RAW264.7 si-ns和RAW264.7 si-SENP1中脂肪酸结合蛋白4（FABP4）mRNA和蛋白的相对表达量。结果 饲喂高胆固醇高脂食物后，油红O染色显示，SENP1+/－ X Apoe－/－小鼠的斑块相对面积（斑块面积/血管总面积）和主动脉弓斑块面积均大于SENP1+/+ X Apoe－/－小鼠，分别为（6.716±1.442）%和（5.952±2.332）%以及（364 249±45 838）和（273 486±158 814）μm2；免疫组织化学染色显示，主动脉根部巨噬细胞面积/斑块面积分别为（41.00±0.05）%和（40.47±0.07）%，差异无统计学意义（P=0.954）。Real-Time PCR和Western blotting检测以及油红O染色结果显示，RAW264-7 si-SENP1的FABP4表达水平及泡沫细胞形成能力均较RAW264-7 si-ns高。结论 SENP1通过下调FABP4的表达,抑制巨噬细胞源性泡沫细胞形成，从而抑制动脉粥样硬化的发生。

关键词: 动脉粥样硬化, 泡沫细胞, SUMO特异性蛋白酶1, 脂肪酸结合蛋白4

Abstract:

Objective To investigate the potential role of SUMO-specific protease 1 (SENP1) in the pathogenesis of atherosclerosis in mice. Methods The development of atherosclerosis in SENP1+/+ X Apoe－/－ mice (n=5) and SENP1+/－ X Apoe－/－ mice (n=4) fed with high cholesterol and high fat diet was observed with whole aorta and aorta root oil red O staining and aorta root immunohistochemical staining of macrophage marker MOMA-2. Acetylated low density lipoprotein (ac-LDL) was used to induce the formation of foam cells and oil red O staining, and the capacities of foam cell formation were compared between RAW264.7 si-ns and RAW264.7 si-SENP1. The relative expression of fatty acid-binding protein 4 (FABP4) mRNA and protein in RAW264.7 si-ns and RAW264.7 si-SENP1 was detected by Real-Time PCR and Western blotting. Results Oil red O staining indicated that after feeding with high cholesterol and high fat diet, the relative atherosclerotic lesion areas (lesion areas/total vessel areas) and aorta arch lesion areas of SENP1+/- X Apoe－/－ mice were significantly larger than those of SENP1+/+ X Apoe－/－ mice [(6.716±1.442) % vs (5.952±2.332)% and (364 249±45 838) μm2 vs (273 486±158 814) μm2]. Immunohistochemical staining revealed that the macrophage area/plaque area in aorta root in SENP1+/- X Apoe－/－ mice and SENP1+/+ X Apoe－/－ mice were (41.00±0.05)% and (40.47±0.07)% respectively, and there was no significant difference between them (P=0.954). Real-Time PCR, Western blotting and oil red O staining demonstrated that FABP4 level and capacity of foam cell formation of RAW264.7 si-SENP1 were significantly higher than those of RAW264.7 si-ns. Conclusion SENP1 may suppress the expression of FABP4 and capacity of foam cell formation of macrophages, thus may inhibit the development of atherosclerosis.

Key words: atherosclerosis, foam cell, SUMO-specific protease 1, fatty acid-binding protein 4