多巴胺D_1类受体在小鼠巨噬细胞上的表达及其对ox-LDL诱导的小鼠巨噬细胞增殖的影响  

Expression of dopamine D_1-like receptors and its role in ox-LDL-induced proliferation in mouse macrophages

作　　者：杨迪[1] 韩愈[1] 寇恂[1] 符金娟[1] 刘渔凯[1] 王震[1] 何多芬[1] 曾春雨[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所心血管内科,重庆市心血管病研究所,重庆400042

出　　处：《第三军医大学学报》2014年第1期11-14,共4页Journal of Third Military Medical University

基　　金：国家自然科学基金(81270338);国家杰出青年科学基金(30925018);重庆市杰出青年科学基金(CSTC 2009BA5044)~~

摘　　要：目的检测小鼠巨噬细胞上的多巴胺D1类受体表达及探讨其对ox-LDL诱导的小鼠巨噬细胞增殖的影响。方法以小鼠巨噬细胞RAW264.7为靶细胞,Western blot法检测多巴胺D1类受体的表达。不同浓度的ox-LDL(10、20、40μg/mL)诱导RAW264.7细胞的增殖,观察在多巴胺受体激动剂(Fenoldopam)10-7mol/L、拮抗剂(SCH23390)10-6mol/L及MAPK信号通路的特异性阻断剂(PD98059)10-6mol/L存在的情况下,RAW264.7增殖的变化情况,细胞增殖用3H-TdR掺入量表示。Western blot法检测磷酸化的ERK、总ERK1/2及增殖细胞核抗原PCNA的表达。结果多巴胺D1类受体在RAW264.7细胞上表达。Fenoldopam(10-7mol/L)、PD98059(10-6mol/L)能明显抑制ox-LDL(20μg/ml)诱导的RAW264.7细胞增殖,且SCH23390(10-6mol/L)预处理可以逆转Fenoldopam(10-7mol/L)对RAW264.7细胞增殖的抑制作用。在MAPK阻断剂PD98059存在的情况下,Fenoldopam作用丧失,此外,Fenoldopam(10-7mol/L)可降低ox-LDL升高的PCNA以及磷酸化ERK水平。结论小鼠巨噬细胞RAW264.7上有多巴胺D1类受体的表达,且刺激多巴胺D1类受体可明显抑制ox-LDL诱导的RAW264.7细胞增殖作用,该作用可能通过影响MAPK/ERK这一信号转导通路来实现。Objective To investigate the expression of dopamine D 1-like receptors in mouse macropha-ges RAW264. 7 and the role of the receptors in ox-LDL-induced proliferation of macrophages. Methods Mouse macrophages RAW264. 7 were used as target cells. Western blotting was used to detect the expression of dopamine D 1-like receptors in RAW264. 7 cells. The RAW264. 7 cells were treated by ox-LDL（ 10,20 and 40 μg / mL） with or without the presence of fenoldopam（ the receptor agonist,10^-7mol / L）,SCH23390（ antagonist,10^-6mol / L） and PD98059（ special inhibitor of MAPK signal pathway,10^-6mol / L）. The proli-feration of RAW264. 7 cells was determined by3H-TdR incorporation,and Western blotting was employed to measure the expression of p-ERK,total ERK1 /2,and proliferation cell nuclear antigen（ PCNA）. Results RAW264. 7 cell expressed D 1-like receptors in mouse macrophages RAW264. 7. Fenoldopam（ 10^-7mol / L） and PD98059（ 10^-6mol / L） significantly inhibited the ox-LDL-induced proliferation of RAW264. 7 cells,and SCH23390（ 10^-6mol / L） reversed the inhibited the proliferation of RAW264. 7 cells pretreated by fenoldpam（ 10^-7mol / L）. In addition,in presence of PD98059,fenoldopam had no effect in this process. Fenoldpam decreased the expression of PCNA and p-ERK which were formerly enhanced by ox-LDL. Conclusion D 1-like receptors are expressed in mouse macrophages,and activation of the receptors reduces ox-LDL-induced proliferation of the cells,which may be through MAPK / ERK signal pathway.

关 键 词：多巴胺D1类受体 巨噬细胞增殖 动脉粥样硬化 

分 类 号：R329.28[医药卫生—人体解剖和组织胚胎学] R392.12[医药卫生—基础医学]