可溶性环氧化物水解酶抑制剂对脂肪细胞胆固醇流出的影响  

The effects of soluble epoxide hydrolase inhibitors on cholesterol effiux in adipocytes

作　　者：蒋云 许丹焰[1] 赵水平[1] 刘颖望[1] 赵婷婷[1] 杜建青[1] 

机构地区：[1]中南大学湘雅二医院心内科,长沙410011 [2]岳阳市第一人民医院老干科,414000

出　　处：《中华内科杂志》2011年第3期235-239,共5页Chinese Journal of Internal Medicine

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-08-566）;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 观察可溶性环氧化合物水解酶抑制剂（sEHi）tAUCB对脂肪细胞胆固醇流出的影响，并探讨其机制。方法 测定脂肪细胞过氧化物酶体增殖物激活受体y（PPARУ）及二磷酸腺苷结合命转运体Al（ABCAl）mRNA及蛋r1的表达，检测细胞内胆同醇流出。结果 tAUCB呈剂量依赖性促进载脂蛋白（Apo）AI介导的胆固醇流出，1、10、50、100μmol／L浓度的tAUCB干预后，胆固醇流出率分别为（5．93±0．66）％，（7．40±0．43）％，（8．30±0．34）％和（9，77±0．42）％。加入10～100μmol／LtAUCB干预组与空白组（5．67±0．17）％比较，胆固醇流出差异有统计学意义（P〈0．05）。同时发现随着tAUCB干预浓度的增加，脂舫细胞ABCAI、PPARУ,mRNA及蛋白的表达也呈剂量依赖性地升高，而GW9662明显抑制tAUCB对脂肪细胞胆固醇流出及ABCAl和PPARУ表达的促进作用。结论 tAUCB可通过上捌PPARУ的表达，促进脂肪细胞Apo A1－ABCAl通路加速细胞内胆固醇流出，抑制脂肪细胞内胆固醇过度蓄积。Objective To observe the effects of soluble epoxide hydrolase inhibitors tAUCB on cholesterol efflux in adipocytes. Methods 3T3-LI preadipocytes were induced to dift）rentiation and maturation. Cells were stimilated with 100 μg/L LPS after starved for 24 hours, then tAUCB in various concentrations（l,10,50,100 μmol/L）were added for 24 h, or incubated with the peroxisome prolilerator activated reeeptor gamnm （PPARУ） antagonist GW9662 （5 μmol/L）. 0 μmol/L tAUCB treated group was taken as empty control. After then, the mRNA expression of PPARУ, and adenosine triphosphate binding cassette transporter A1 （ ABCAI ） in cells were determined via realtime-PCR, the amounts of protein expression of PPARУ,and ABCA1 in cells were detected by Western blot, the eMux rates of 3 H-cholesterol in cells were detected hy means of liquid scintillation counter. Results tAUCB could dose-dependently increase the apolipoprotein A 1 （ apoA1 ） -mediated cholesterol efflux in adipocytes. After stimulated by 1 , 10, 50,100 μmol/L tAUCB, cholesterol efflux rates were （5.93±0.66）%, （7.40± 0.43）%, （8.30 ±0. 34）% , （9. 77 ± 0.42 ）% respectively, there were significant difference after treated by 10-100 μmol/L tAUCB compared with control（5.67 ± 0. 17 ） % （ P 〈 O. 05 ）. With the concentration of tAUCB increased, ABCA1, PPARУ mRNA and protein expression were also dose-dependently up-regulated. GW9662 could significantly inhibit the effects of tAUCB, and then reduce the cholesterol ettlux and the expression of PPARУ and ABCAI in adipocytes. Conclusions tAUCB could up-regulate PPARУ expression in adipocytes, and promote the cholesterol efflux of adipoeytes via apoAI-ABCA1 pathway, which might decrease the cellular cholesterol accumulation in adipocytes.

关 键 词：脂细胞 胆固醇 可溶性环氧化合物水解酶抑制剂 

分 类 号：R96[医药卫生—药理学]