SUMO特异性蛋白酶1在动脉粥样硬化发病机制中的作用  

Role of SUMO-specific protease 1 in pathogenesis of atherosclerosis

作　　者：黄弦[1] 吴际[1] 程金科[2] 

机构地区：[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　　处：《上海交通大学学报（医学版）》2012年第8期1056-1061,共6页Journal of Shanghai Jiao tong University:Medical Science

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+/-XApoe-/-(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。Objective To investigate the potential role of SUMO-specific protease I （SENPI） in the pathogenesis of atherosclerosis in mice. Methods The development of atheroselerosis 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） μm^2 vs （273 486 ± 158 814） ~m2]. Immunohistochemical staining revealed that the macrophage area/ plaque area in aorta root inSENP1^＋/^＋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 RAW264.7si-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.

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 

分 类 号：R541.4[医药卫生—心血管疾病] R-332[医药卫生—内科学]