低密度脂蛋白影响巨噬细胞的SAPK信号通路  

Study on signal pathway on function changing of macrophages induced by oxidized low density lipoprotein

作　　者：卢次勇[1] 凌文华[1] 马静[1] 唐志红[1] 吴聪娥[1] 

机构地区：[1]中山大学公共卫生学院医学统计与流行病学系,广州510080

出　　处：《中国公共卫生》2003年第10期1171-1173,共3页Chinese Journal of Public Health

基　　金：国家杰出青年科学基金资助 ( 30 0 2 50 37);广东省自然科学基金资助 ( 990 0 90 )

摘　　要：目的　研究氧化型低密度脂蛋白 (oxidizedlowdensitylipoprotein ,Ox -LDL)对巨噬细胞增殖、坏死及凋亡影响的非清道夫受体途径 ,及对应激活化蛋白激酶 (stress -activatedproteinkinase ,SAPK)信号通路的影响。 方法　采用 3个时间水平 (2 4,48,72h)、4个剂量水平 (0 ,50 ,10 0 ,2 0 0mg/L)的两因素析因设计 ,观察Ox -LDL对清道夫受体A(scavengerreceptorA ,SRA)基因敲除小鼠巨噬细胞增殖、坏死及凋亡影响的时间、剂量效应关系 ;Ox -LDL对该细胞SAPK活性的影响。结果　Ox -LDL可诱导SRA基因敲除小鼠巨噬细胞增殖、凋亡及坏死 ,并与其作用浓度和剂量相关 (P <0 0 1) ,同时Ox -LDL可引起SAPK活性水平发生变化。结论　Ox -LDL对SRA基因敲除小鼠腹腔巨噬细胞的影响主要为诱导增殖作用 ,高浓度时伴有一定致凋亡、坏死作用 ,其致细胞增殖、凋亡作用可能部分与SAPK信号途径有关 ,提示非清道夫受体途径在OxObjective To study the effects of oxidized low density li poprotein on proliferation,apoptosis and necrosis of macrophages via the possibl e mechanism of signal transduction unrelated to scavenger receptor pathway.The r ole of SAPK(Stress-activated protein kinase) signal pathway were studied. Methods Two-factorial experiment was designed to explore the influence of four dosage levels of Ox-LDL (0,50,100,200?mg/L) at three diff erent stages of exposure (24,48 and 72?hr) on proliferation apoptosis and necro sis of macrophage cells of SRA (scavenger receptor A) knockout mice.Activity of SAPK in the macrophage cells of SRA knockout mice was observed with different ex posure level of Ox-LDL at different times.Results The apoptosis and necrosis of macrophages of SRA knockout mice induced by Ox-LDL was associated with both the exposure level and time ( P <0.01); Ox-LDL could induced the proliferation of the macrophages of SRA knockout mice,which was significantly associated with the dosage and time ( P <0.01).The activities of SAPK were changed at different dose of Ox-LDL. Conclusion Proliferation was the main response to Ox-LDL, and apoptosis and necrosis were also observed for higher exposure of Ox-LDL in m acrophages of SRA knockout mice.This proliferation and apoptosis induced by Ox-L DL might be partly mediated by SAPK signal pathways,which implicated that other ways might play the role in the Ox-LDL induced proliferation and apoptosis of ma crophage with scavenger receptor deficiency.

关 键 词：氧化型低密度脂蛋白 巨噬细胞 信号转导 凋亡 坏死 

分 类 号：R543.5[医药卫生—心血管疾病] R114[医药卫生—内科学]