格列本脲对泡沫细胞形成的影响  

Effects of glibenclamide on the formation of foam cells

作　　者：何平[1] 成蓓[1] 王洪星 戚本玲[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院,湖北武汉430022 [2]美国Zeneca制药公司分子和细胞生物学部,美国19850

出　　处：《中国医院药学杂志》2007年第3期312-315,共4页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金资助项目(编号:30170378)

摘　　要：目的:研究格列本脲(glibenclamide)对THP-1单核巨噬细胞形成泡沫细胞的影响及机制。方法:体外培养人THP-1单核细胞系,由佛波酯(PMA)作用使其分化为巨噬细胞,后者再由乙酰化低密度脂蛋白(Ac-LDL)进行脂质负荷转变为泡沫细胞。不同质量浓度的格列本脲单独或与Ac-LDL共同作用于上述巨噬细胞,以放射性同位素标记底物法检测酰基辅酶A:胆固醇酰基转移酶(ACAT)活性的变化,油红O染色法检测泡沫细胞的形成,酶比色法检测细胞中的总胆固醇、游离胆固醇和胆固醇酯含量。结果:格列本脲使脂质负荷的巨噬细胞转变为泡沫细胞的数目减少,并明显抑制脂质负荷前后巨噬细胞中ACAT酶活性;随着格列本脲剂量增加,脂质负荷前后的巨噬细胞中胆固醇酯含量逐渐降低,呈剂量依赖性趋势。结论:格列本脲抑制泡沫细胞形成,其作用机制可能与其抑制ACAT酶活性和细胞中胆固醇酯含量有关。OBJECTIVE To study the effects and mechanism of glibenclamide on the formation of foam cells in THP-1 cells. METHODS The THP-1 cells were cultured and differentiated into macrophages by phorbol myristate acetate （PMA）. The macrophages were incubated with acetyled LDL （Ac-LDL） to generate foam cells. Glibenclamide was added in various doses on macrophages treated with or without Ac-LDL. The foam cells were determined by oil O staining. The acyl coenzyme A： cholesterol acyltransferase （ACAT） activity was measured by quantifying the incorporation of [1-^14C] oleoyl CoA into eholesteryl esters. An enzymatic colorimetric assay was used to determine cell cholesterol mass. RESULTS The numbers of foam cells were decreased by glibenclamide. Glibenclamide significantly inhibited the activity of ACAT in THP-1 macrophages with or without Ac-LDL treatment. The cholesteryl esters （CE） mass decreased with the increasing doses of glibenelamide in macrophages with or without Ac-LDL treatment,the inhibiting effect was in a dose- dependant manner. CONCLUSION Glibenclamide inhibited the formation of foam cells. It may be the results of inhibits effect of activity of ACAT and the CE mass by glibenclamide.

关 键 词：酰基辅酶A 胆固醇酰基转移酶 格列本脲 胆固醇 泡沫细胞 

分 类 号：R965[医药卫生—药理学]