中文摘要：

目的探讨过氧化物酶体增殖物激活受体-γ（PPAR-γ）对巨噬细胞中酰基辅酶A：胆固醇酰基转移酶-1（ACAT-1）表达影响及可能参与的信号途径。方法在RPMI1640培养基中培养人单核细胞（THP-1）,加入佛波酯（PMA）培养48h,细胞贴壁呈巨噬细胞样分化。在高浓度胰岛素状态下,分别加入PPAR-γ的配体罗格列酮和胰岛素信号途径阻滞剂[细胞外信号调节激酶（ERK）抑制剂PD98059、p38促分裂原活化蛋白激酶（p38MAPK）抑制剂SB203580和c-Jun氨基末端激酶（JNK）抑制剂SP600125],采用Western-blot法检测巨噬细胞ACAT-1蛋白水平,实时定量PCR法检测ACAT-1mRNA水平。结果在高胰岛素状态下,给予罗格列酮干预后ACAT-1mRNA和蛋白表达均降低;再加入SB203580后ACAT-1mRNA和蛋白表达较加入罗格列酮时均增加。结论p38MAPK途径参与了PPAR-γ抑制ACAT-1的表达,并发挥抗动脉粥样硬化的作用。

英文摘要：

Objective To investigate the effects of peroxisome proliferator activated receptors-γ（PPAR-γ）on Acyl-CoA：cholesterol acyltransferases-1（ACAT-1）expression in human macrophages and the possible signaling pathways.Methods Human monocytes（THP-1）were cultured in RPMI1640 and induced differentiation into macrophages in the present of phorbol myristate acetate（PMA）for 48 hours.Under high insulin level,the macrophages were treated with PPAR-γ activated by rosiglitazone and the inhibitors of insulin signaling pathway [PD98059,an inhibitor of extracellular signal-regulated kinase（ERK）;SB203580,an inhibitor of p38 mitogen-activated protein kinase（p38MAPK）;SP600125,an inhibitor of c-Jun N-terminal kinase（JNK）],then the ACAT-1 protein expression and ACAT-1mRNA level were determined by Western-blot and real-time quantitative polymerase chain reaction respectively.Results Both the ACAT-1 mRNA level and the ACAT-1 protein expression decreased after treated with rosiglitazone,and increased after the treatment of p38MAPK inhibitor SB203580.Conclusions p38MAPK signaling pathway involves in the inhibition of ACAT-1 expression caused by PPAR-γ,which may play an important role in fighting back the human atherogenesis.