血浆脂蛋白(a)对巨噬细胞摄取乙酰化低密度脂蛋白的影响

目的　研究血浆脂蛋白 (a) [lipoprotein(a) ,Lp(a) ]对巨噬细胞结合 ,摄入及降解乙酰化低密度脂蛋白 (acetylatedlowdensitylipoprotein ,Ac LDL) ,清道夫受体 A (scavengerreceptor A ,ScR A)和ScR B的影响。方法　利用人类单核细胞株 (THP 1细胞 )源的巨噬细胞培养 ,受体摄取配体及Northern印迹方法 ,观察Lp(a)对巨噬细胞受体摄取Ac LDL以及对巨噬细胞ScR A和ScR BmRNA表达的影响。结果　THP 1细胞源的巨噬细胞对Ac LDL的结合量随Lp(a)浓度 (0 ,10 ,2 5 ,5 0及 10 0 μg/ml)的增加而增加 ,而天然LDL对此无影响。与对照组比较 [Lp(a)非投用组 ],投用 5 0μg/mlLp(a)时 ,巨噬细胞对Ac LDL结合量 (binding)增加 2 6 9.2 5 %(P <0 .0 1) ,对Ac LDL的摄入量 (uptake)增加5 9.46 %(P <0 .0 1) ,对Ac LDL的降解量 (degradation)增加 5 5 .77%(P<0 .0 1) ,且巨噬细胞ScR AmRNA表达明显增强 ,与对照组 [Lp(a)非投用组 ]比较增强 43.5 6 %,而Lp(a)并不影响ScR BmRNA的表达。结论　Lp(a)可增加THP 1细胞源的巨噬细胞结合、摄入及降解Ac LDL ,这种作用可能通过Lp(a)增强巨噬细胞ScR A基因的表达来实现。

Influence of plasma lipoprotein(a) on uptake of acetylated low density lipoprotein in THP-1 derived macrophages

Objective To investigate whether lipoprotein(a) can influence uptake of acetylated low density lipoprotein (Ac-LDL) and scavenger receptor-A(ScR-A) and ScR-B expression in macrophages.Methods 12-O-tetradecanoylphobol-13-acetate was used for THP-1 monocytes differentiation into macrophages.THP-1 derived macrophages were treated with different concentrations of Lp(a)(0,10,25,50,and 100 μg/ml) and their uptake of Ac-LDL (including 4℃ binding,37℃ uptake and 37℃ degradation),ScR-A mRNA and ScR-B mRNA expressions were measured.Results Ac-LDL binding was increased with increasing Lp(a) concentration from 0 to 100 μg/ml,but it was not influenced by native LDL.Compared with the control [non Lp(a) treated group],Ac-LDL binding,uptake and degradation was increased by 269.25%(P<0.01), 59.46% (P<0.01) and 55.77%(P<0.01), respectively and ScR-A mRNA expression was augmented by 43.56% in macrophages after treatment with 50 μg/ml Lp(a),whereas ScR-B mRNA expression was not affected by Lp(a).Conclusions Lp(a) can increase Ac-LDL uptake in macrophages through up-regulation of macrophage ScR-A expression and this mechanism may contribute to progress of atherogenesis and atherosclerosis.