[1]蒙颖,徐芳,王志禄,等.罗格列酮对泡沫细胞中胆固醇贮存与运输相关蛋白ACAT-1、ABCA-1表达的影响[J].第三军医大学学报,2012,34(22):2288-2291.
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
34卷
期数:
2012年第22期
页码:
2288-2291
栏目:
论著
出版日期:
2012-11-30

文章信息/Info

Title:
Effect of rosiglitazone on expression of acyl-coenzyme A cholesterol acyltransferase 1 and ATP-binding cassette transporter A1 in foam cells
作者:
蒙颖; 徐芳; 王志禄; 李万玲; 贾军正; 郭文芬; 谢宛霞; 胡海英; 胡旭堂
兰州大学：第一临床医学院心内科，第一医院心内科
Author(s):
Meng Ying;  Xu Fang;  Wang Zhilu;  Li Wanling;  Jia Junzheng;  Guo Wenfen;  Xie Wanxia;  Hu Haiying;  Hu Xutang
Department of Cardiology, First Clinical Medical College of Lanzhou University,Department of Cardiology, First Hospital of Lanzhou University, Lanzhou, Gansu Province, 730000, China
关键词:
罗格列酮; 泡沫细胞; 胆固醇; 动脉粥样硬化
Keywords:
rosiglitazone;  foam cell;  cholesterol;  atherosclerosis
分类号:
R543.5；R966；R977.15
文献标志码:
A
摘要:
目的      观察罗格列酮对RAW264.7巨噬源性泡沫细胞形成中胆固醇含量及酰基辅酶A-胆固醇酰基转移酶-1（acyl coenzyme A cholesterol acyl transfer enzyme 1，ACAT-1）、三磷酸腺苷结合盒转运蛋白A-1 （ATP combination box of transporter 1，ABCA-1） 表达的影响，探讨罗格列酮对泡沫细胞形成的影响及可能的作用机制。      方法      在DMEM高糖培养基中培养RAW264.7巨噬细胞，按完全随机分组方法分为：①空白对照组（常规培养基培养巨噬细胞）；②氧化低密度脂蛋白（oxidized low density lipoprotein，oxLDL）组（用终浓度为30 mg/L的oxLDL孵育48 h）；③oxLDL+罗格列酮组（分别用终浓度5、10、20 μmol/L的罗格列酮+30 mg/L oxLDL共同孵育48 h）（n=10）。采用油红O染色观察泡沫细胞，胆固醇检测试剂盒测定各组细胞内总胆固醇（total cholesterol，TC）和游离胆固醇（free cholesterol，FC）的含量，Western blot法检测各组细胞ACAT-1和ABCA1的表达水平。      结果      oxLDL组中大量泡沫细胞的胞质被油红O染色，oxLDL+罗格列酮组泡沫细胞胞质染色明显浅于oxLDL组的细胞；与oxLDL组相比，oxLDL＋罗格列酮组TC及FC显著降低（P<0.05），且呈浓度依赖性；Western blot检测结果表明，不同浓度（5、10、20 μmol/L）oxLDL＋罗格列酮组ACAT-1蛋白表达分别为（0.94±0.11）、（0.86±0.13）、（0.58±0.12），与oxLDL组（1.19±0.12）相比有显著差异（P<0.05），不同浓度oxLDL＋罗格列酮组ABCA1蛋白表达分别为（0.72±0.08）、（0.91±0.15）、（1.15±0.11），与oxLDL组（0.63±0.05）相比有显著差异（P<0.05），且呈浓度依赖性。      结论      罗格列酮可能通过抑制ACAT-1的表达及促进ABCA-1的表达减少泡沫细胞形成，从而发挥其抗动脉粥样硬化的作用。
Abstract:
Objective      To investigate the effect of rosiglitazone on cholesterol content and the expression of acyl-coenzyme A cholesterol acyltransferase 1 (ACAT1) and ATP-binding cassette transporter A1 (ABCA1) in RAW264.7 macrophage-derived foam cells, and to explore the mechanism of rosiglitazone in foam cell formation.       Methods      Mouse macrophage RAW264.7 cells were cultured in high-glucose DMEM and were randomly divided into a control group, an oxidized low-density lipoprotein (oxLDL) group, in which cells were incubated with 30 mg/L oxLDL for 48 h, and an oxLDL+rosiglitazone group, in which cells were incubated with 30 mg/L oxLDL plus 5, 10 and 20 μmol/L rosiglitazone for 48 h, respectively (n=10). The formation of foam cells were identified by oil red O staining. The levels of intracellular total cholesterol (TC) and free cholesterol (FC) in each group were determined by a cholesterol detection kit, and the expression of ACAT-1 and ABCA-1 protein was determined by Western blotting.       Results      Mouse macrophage RAW264.7 cells in the oxLDL group were stained by oil red O, but the color of the macrophages in the oxLDL+rosiglitazone group was lighter than that in the oxLDL group. Compared with the oxLDL group, the contents of intracellular TC and FC in the oxLDL+rosiglitazone group significantly decreased (P<0.05) in a dose-dependent manner. Western blot results showed the expression levels of ACAT-1 in the oxLDL+rosiglitazone group with different concentrations of rosiglitazone (5, 10 and 20 μmol/L) were (0.94±0.11), (0.86±0.13) and (0.58±0.12), respectively, which were significantly different from that in the oxLDL group (1.19±0.12) (P<0.05). The expression levels of ABCA-1 in the oxLDL+rosiglitazone group with different concentrations of rosiglitazone (5, 10 and 20 μmol/L) were (0.72±0.08), (0.91±0.15) and (1.15±0.11), respectively, which were also significantly different from that in the oxLDL group (0.63±0.05) (P<0.05).       Conclusion      Rosiglitazone may inhibit foam cell formation by decreasing the expression of ACAT-1 and increasing the expression of ABCA-1, which plays an important role in inhibiting atherosclerosis.

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更新日期/Last Update: 2012-11-20