氧化型低密度脂蛋白诱导巨噬细胞内源性大麻素系统激活  

Activation of Endocannabinoid System in Macrophages by Stimuli of Oxidized Low Density Lipoprotein

作　　者：江立生[1,2] 卜军[2] 胡刘华[2] 韩志华[2] 沈玲红[2] 何奔[2] 

机构地区：[1]上海交通大学医学院附属仁济医院老年病科,上海市200127 [2]上海交通大学医学院附属仁济医院心血管内科,上海市200127

出　　处：《中国动脉硬化杂志》2009年第1期19-22,共4页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金(30600242和30670880)资助

摘　　要：目的探讨氧化型低密度脂蛋白刺激能否诱导巨噬细胞内源性大麻素系统激活。方法体外常规培养RAW264.7小鼠巨噬细胞,加入氧化型低密度脂蛋白或溶媒孵育24 h,用高效液相色谱分析技术检测巨噬细胞内源性大麻素Anandamide和2-arachidonoylglycerol水平,以实时定量PCR技术和免疫印迹法对大麻素CB1、CB2受体和血小板活化因子受体mRNA和蛋白的表达进行分析。结果内源性大麻素2-arachidonoylglycerol水平在6mg/L和12 mg/L氧化型低密度脂蛋白刺激时分别升高了2.4倍和4.8倍,而Anandamide水平无明显变化。3～12mg/L氧化型低密度脂蛋白刺激时,RAW264.7巨噬细胞大麻素CB1和CB2受体及血小板活化因子受体mRNA和蛋白的表达均明显上调(P<0.01)。结论首次证实氧化型低密度脂蛋白通过激活血小板活化因子受体诱导巨噬细胞内源性大麻素系统激活,提示氧化型低密度脂蛋白致动脉粥样硬化过程中可能涉及该系统的激活。Aim To investigate whether the endocannabinoid system in macrophages is activated by oxidized low density lipoprotein （ox-LDL） stimuli or not. Methods RAW264.7 mouse macrophages were cultured with or without ox-LDL. Production of the endocannabinoid anandamide （AEA） and 2-arachidonoylglycerol （2-AG） was quantified by liquid chromatography/mass spectrometry （LC/MS）. Real time PCR and Western blotting analysis were also performed to measure expressions of the cannabinoid receptors （ CB1 and CB2 ） mRNA and protein and expressions of platelet activating factor receptor （ PAF-R ） mRNA and protein. Results Ox-LDL increased significantly the cellular level of 2-AG, with an increase of 2.4-fold at 6 mg/L ox-LDL and an increase of 4.8-fold at 12 mg/L ox-LDL, whereas AEA level had no obvious change. Stimuli of 3 - 12 mg/L of ox-LDL resulted in significant increases in cannabinoid CB1 and CB2 receptor mRNA and protein expressions （ P 〈 0.01 ）. Ox-LDL（ 1 - 12 mg/L） further upregnlated the PAF-R mRNA and protein expressions. Conclusion Ox-LDL stimuli induces the endocannabinoid system activation by PAF-R pathway, which indicates that this system activation might be involved in the proatherogenic activities of ox-LDL.

关 键 词：内源性大麻素 氧化型低密度脂蛋白 血小板活化因子受体 巨噬细胞 动脉粥样硬化 

分 类 号：R5[医药卫生—内科学]