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阻断MaxiK通道对人单核细胞源性巨噬细胞向泡沫细胞分化的抑制作用 被引量：2

Inhibitory effect of blocking MaxiK channel on human monocyte-derived macrophages differentiation into foam cells
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摘要 目的研究高电导钙离子激活钾通道(MaxiK通道)在人单核细胞源性巨噬细胞向泡沫细胞分化的过程中,其mRNA和蛋白的表达及作用。方法采用密度梯度离心加贴壁黏附法,从男性健康志愿者的外周血中分离单核细胞,经5d培养后分化为巨噬细胞。在建立人巨噬细胞源性泡沫细胞模型的基础上,采用免疫细胞化学染色法、RT-PCR及蛋白印迹,研究MaxiK通道α-亚单位的表达,并观察其特异性阻断剂-Paxilline对摄取氧化型低密度脂蛋白(OxLDL)的巨噬细胞中胆固醇代谢的影响。结果将巨噬细胞同30mg/LOxLDL于37℃孵育60h后,细胞体积增大,并有许多红色的脂质颗粒沉积于细胞质内,细胞内的总胆固醇(TC)、游离胆固醇(FC)及胆固醇酯(CE)的含量均显著增加,CE/TC从(14.437±6.781)%提高到(57.946±3.507)%(n=7,P<0.05);而MaxiK通道α-亚单位mRNA及蛋白的表达水平没有明显改变(P>0.05)。5和10μmol/L的Paxilline能显著减少巨噬细胞内TC、FC及CE的含量,CE/TC分别降至(41.217±5.584)%和(18.017±11.559)%(n=7,P<0.05),细胞内沉积的红色脂质颗粒也明显减少。结论阻断MaxiK通道能抑制人单核细胞源性巨噬细胞向泡沫细胞分化。 AIM： To investigate the expression of highconductance Ca^2＋-activated potassium channel （Maxik channel） mRNA and protein during human monocyte-derived macrophage differentiation into foam cells and its function in foam cell formation. METHODS： Human peripheral blood monocytes were isolated from healthy male volunteers by density gradient centrifugation and then by adherent method. The obtained monocytes were cultured for 5 days to differentiate into macrophages. Based on establishment of human macrophage-derived foam cells model, the expression of MaxiK channel α-subunit was investigated by immunocytochemical staining, RT-PCR and Western blot. Furthermore, the effect of Paxilline, a MaxiK channel-specific inhibitor, on cholesterol metabolism in macrophages incepting oxidized low density lipoprotein （OxLDL） was studied. RESULTS： After the macrophages co-incubated with 30 mg/L OxLDL at 37℃ for 60 hours, the cellular volume obviously enlarged and many red lipid granules were deposited in cytoplasm. The total amount of cholesterol （TC）, free cholesterol （FC） and cholesterol ester （CE） in cells markedly increased and the ratio of CE/TC rose from （14.437±6.781）% to （57.946±3.507）% （n=7, P〈0.05）. However, the expression of MaxiK channel α-subunit had no significant change （ P 〉 0.05 ）. Paxilline （5μmol/L and 10μmol/L） markedly reduced the content of TC, FC and CE in macrophages and the ratio of CE/TC decreased to （41.217±5.584 ） % and （18.017±11.559 ） %, respectively （ n = 7, P 〈0.05 ）. Meanwhile, the red lipid granules deposited in the cytoplasm of macrophages also decreased. CONCLUSION. Blocking MaxiK channel can inhibit human monocyte-derived macrophage to be differentiated into foam cells.
作者 雷新军 马爱群 席雨涛 张葳 姚艳 杜媛
机构地区 西安交通大学医学院第一附属医院心血管内科
出处 《细胞与分子免疫学杂志》 CAS CSCD 北大核心 2006年第3期310-313,共4页 Chinese Journal of Cellular and Molecular Immunology
基金 美国中华医学基金会资助项目(No.#01-761) 科技部国际合作项目(No.2003DF000037)
关键词 离子通道 脂蛋白 细胞分化 动脉粥样硬化 ion channel lipoprotein cell differentiation atherosclerosis
分类号 R363.21 [医药卫生—病理学]
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细胞与分子免疫学杂志
2006年 第3期

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