肝X受体激动剂对人THP-1细胞三磷酸腺苷结合盒转运体A1和肝X受体α、β亚型表达的影响

Effects of Liver X Receptors Agonists on the Expression of ATP-Binding Cassette Transporter A1, Liver X Receptors α and Liver X Receptors β mRNA in THP-1 Cells

目的 研究肝X受体激动剂3β- 羟基- 5α,6α- 环氧胆烷酸甲酯和进口肝X受体激动剂激动剂T 0 90 1317对THP 1细胞三磷酸腺苷结合盒转运体A1、肝X受体激动剂α和肝X受体激动剂β亚型mRNA表达的影响。方法 应用逆转录—聚合酶链反应检测- 3β- 羟基- 5α,6α- 环氧胆烷酸甲酯和T 0 90 1317作用前后THP 1细胞源性巨噬细胞三磷酸腺苷结合盒转运体A1、肝X受体激动剂α和肝X受体激动剂β的mRNA表达,免疫组织化学检测三磷酸腺苷结合盒转运体A1蛋白水平的表达。结果 3β- 羟基- 5α,6α- 环氧胆烷酸甲酯和T 0 90 1317均能显著上调THP 1细胞中三磷酸腺苷结合盒转运体A1和肝X受体激动剂α的mRNA表达(P <0 .0 1) ,并呈时间和剂量依赖性;在对肝X受体激动剂β表达的影响方面,低浓度的T 0 90 1317能明显上调肝X受体激动剂β的表达,而3β- 羟基- 5α,6α-环氧胆烷酸甲酯只有在较高浓度时(10 μmol/L)才表现出上调肝X受体激动剂β表达的作用(P <0 .0 5 )。结论 3β羟基- 5α,6α-环氧胆烷酸甲酯以激动肝X受体激动剂α为主,并与T 0 90 1317一样,可上调THP 1细胞中三磷酸腺苷结合盒转运体A1和肝X受体激动剂α的表达。

Aim To evaluate the effects of Methyl 3β-hydroxy-5α, 6α-epoxycholanate (MHEC) and T-0901317 on the expression of ATP-binding cassette transporter A1 (ABCA1), liver X receptors (LXR)αand LXR β in THP-1 cells. Methods THP-1 cells were cultured and treated with LXRs agonists MHEC and T-0901317 respectively. The mRNA expressions of ABCA1, LXRα and LXRβ were detected by reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical method was used to assess the expression of ATP-binding cassette transporter A1 protein in the cells. Results Both of the two LXR agonists' treatment significantly increased ABCA1 mRNA and LXRα mRNA in a time and dose-dependent fashion in THP-1 cells. The expression of ATP-binding cassette transporter A1 protein also increased in the treated cells. While the LXRβ expression in T-0901317 group was stronger than in MHEC group. Conclusions Both MHEC and T-0901317 can up-induce the expressions of ATP-binding cassette transporter A1 and LXRα in THP-1 cells, and MHEC is more likely to be a selective agonist to LXRα.