可溶性环氧化物水解酶抑制剂t-AUCB对巨噬细胞脂质代谢的影响  

Effects of Soluble Epoxide Hydrolase Inhibitors t-AUCB on Lipid Metabolism in Mouse Macrophage

作　　者：赵婷婷[1] 沈莉[1] 赵旋[1] 许丹焰[1] 赵水平[1] 

机构地区：[1]中南大学湘雅二医院,湖南省长沙市410011

出　　处：《中国动脉硬化杂志》2012年第4期295-299,共5页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金(30770856);教育部新世纪优秀人才支持计划(NCET-08-0566);湖南省自然科学基金(10JJ3026);中南大学代谢与内分泌研究所基金(DY-2008-02-04)

摘　　要：目的观察可溶性环氧化物水解酶抑制剂t-AUCB对小鼠巨噬细胞脂质摄取及降解的影响,并探明其可能机制。方法培养小鼠巨噬细胞RAW264.7,分别用不同浓度t-AUCB(1、10、50及100μmol/L)干预24 h,或在100μmol/L t-AUCB干预前1 h加入PPARγ拮抗剂GW9662 5μmol/L,采用t-AUCB 0μmol/L干预组作为空白对照。采用125Ⅰ-ox-LDL放射配基法测定小鼠巨噬细胞对氧化型低密度脂蛋白(ox-LDL)的摄取及降解,实时荧光定量PCR和Western blot分别测定小鼠巨噬细胞CD36 mRNA和蛋白表达。结果 t-AUCB呈剂量依赖性地增加巨噬细胞125Ⅰ-ox-LDL摄取量和降解量,0、1、10、50和100μmol/L t-AUCB干预时,摄取量分别为414.96±46.71μg/g、519.54±47.7μg/g、629.04±37.97μg/g、720.66±48.58μg/g和881.57±68.44μg/g,降解量分别为16180.23±967.28μg/g、17369.62±478.34μg/g、21794.85±689.36μg/g、27883.03±712.25μg/g和30194.61±635.71μg/g,与空白对照组比较差异显著(P<0.05),加入GW9662后100μmol/L组摄取量降至467.80±51.98μg/g,降解量降至16326.19±735.95μg/g,与单独加入t-AUCB组比较差异具有显著性(P<0.05);t-AUCB可呈剂量依赖性的增加小鼠巨噬细胞CD36 mRNA和蛋白的表达,而加入GW9662后明显抑制上述作用。结论 t-AUCB可通过上调PPARγ-CD36信号通路分子表达增加小鼠巨噬细胞摄取和降解ox-LDL。Aim To observe the effects of soluble epoxide hydrolase inhibitors t-AUCB on the uptake and degradation of lipid in mouse macrophage. Methods RAW264. 7 mouse macrophage was cultured, then t-AUCB in various concentration（ 1, 10, 50 and 100 μmol/L） were added for 24 hours, or incubated with peroxisome proliferators activated receptor gamma （PPARγ） antagonist GW9662 （5 μmol/L）. 0 μmol/L t-AUCB treated group was taken as empty control. After then, the uptake and degradation of oxidized low density lipoprotein （ox-LDL） in cells were detected by radioligand assay. The mRNA and protein expression of CD36 were determined by real-time PCR and Western blot. Resuits t-AUCB could dose-dependently increase the uptake and degradation of ox-LDL in mouse macrophage. After stimulated with 0, 1, 10, 50 and 100 μmol/L t-AUCB, the uptake level of ox-LDL were 414. 96 ±46. 71 p,g/g, 519. 54 ± 47.7 μg/g, 629. 04 ±37.97 μg/g,720. 66± 48. 58 μg/g, 881.57 ± 68.44 μg/g, and the degradation of ox-LDL were 16180. 23 ±967.28 μg/g, 17369. 62 ±478. 34μ/g, 21794. 85 ±689. 36 μg/g, 27883.03 ±712. 25 μg/g, 30194. 61 ± 635.71 μg/g. However, after incubation of GW9662, the uptake and degradation of ox-LDL with 100 μmol/L t-AUCBwere decreased to 467.80 ± 51.98 μg/g and 16326. 19 ± 735.95 μg/g. Respectively, the difference was statistically significant （ P 〈 0. 05 ）. t-AUCB could dose-dependently increase the mRNA and protein expression of CD36, but after add- ed with GW9662, above-mentioned function was significantly attenuated. Conclusion t-AUCB could upregulate the uptake and degradation of ox-LDL in mouse macrophage through PPARγ-CD36 pathway.

关 键 词：巨噬细胞 可溶性环氧化物水解酶抑制剂 氧化型低密度脂蛋白 CD36 

分 类 号：R363[医药卫生—病理学]